Malenović, Anđelija

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orcid::0000-0002-4102-3933
  • Malenović, Anđelija (140)
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Author's Bibliography

Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline

Stojanović, Jevrem; Zalewski, P.; Otašević, Biljana; Zečević, Mira; Malenović, Anđelija; Janošević-Ležaić, Aleksandra; Ranđelović, D.; Protić, Ana

(Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu, 2023)

TY  - CONF
AU  - Stojanović, Jevrem
AU  - Zalewski, P.
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Malenović, Anđelija
AU  - Janošević-Ležaić, Aleksandra
AU  - Ranđelović, D.
AU  - Protić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5479
AB  - In the last two decades, there has been a growing awareness of the presence of pharmaceuticals in the aquatic 
environment. Antibiotics are particularly alarming because their occurrence may result in increased antibiotic 
resistance. Difficulties in sample preparation and removal of low concentrations of pharmaceuticals from 
environmental water could be overcome by their adsorption onto novel, non-polluting, and inexpensive 
materials. 
In this study, biochar prepared by pirolysis of biomass at 500°C (BC500) and 800°C (BC800) and activated 
carbon prepared upon treatment with ZnCl2 at 800°C (AC800) were evaluated as potential adsorbents. Ailanthus 
altissima was selected as a source of raw material, leaf, because it is a widespread invasive tree that negatively 
affects biodiversity. Tetracycline hydrochloride was selected as a model substance, since it is an antibiotic 
widely present in environmental water. Central composite design was employed to simultaneously investigate 
the effects of adsorbate solution pH, ionic strength (KCl concentration), and adsorbent mass on removal 
efficiency of all three adsorbents, and to find optimal conditions for studying adsorption kinetics and equilibrium 
on the most promising adsorbent. The removal efficiency and adsorbed mass were calculated from the HPLC UV determined concentration of tetracycline post-adsorption. 
Under optimal conditions (10.18 mg of adsorbent, pH 4.42, and ionic strength 165mM), AC800 showed the 
highest affinity for tetracycline, i.e. 38.22% removal and adsorbed mass of 56.32 mg g-1 compared to 14.57% 
and 21.48 mg g-1 (BC500) and 18.82% and 27.73 mg g-1 (BC800). Removal efficiency of AC800 was strongly 
influenced by the adsorbent mass and solution pH. The kinetics study showed a rapid adsorption process 
(equilibrium attained in 120 minutes), while equilibrium studies revealed a high adsorption capacity for 
tetracycline (131.55 mg g-1). AC800 has been shown to be a promising novel drug adsorbent and should be 
further tested for its suitability in water treatment and sample preparation.
PB  - Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu
PB  - Polskie Towarzystwo Farmaceutyczne
PB  - Stowarzyszenie Stop Nielegalnym Farmaceutykom
C3  - IV Poznańska Konferencja  Naukowo – Szkoleniowej, 23-24.10.
T1  - Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5479
ER  - 
@conference{
author = "Stojanović, Jevrem and Zalewski, P. and Otašević, Biljana and Zečević, Mira and Malenović, Anđelija and Janošević-Ležaić, Aleksandra and Ranđelović, D. and Protić, Ana",
year = "2023",
abstract = "In the last two decades, there has been a growing awareness of the presence of pharmaceuticals in the aquatic 
environment. Antibiotics are particularly alarming because their occurrence may result in increased antibiotic 
resistance. Difficulties in sample preparation and removal of low concentrations of pharmaceuticals from 
environmental water could be overcome by their adsorption onto novel, non-polluting, and inexpensive 
materials. 
In this study, biochar prepared by pirolysis of biomass at 500°C (BC500) and 800°C (BC800) and activated 
carbon prepared upon treatment with ZnCl2 at 800°C (AC800) were evaluated as potential adsorbents. Ailanthus 
altissima was selected as a source of raw material, leaf, because it is a widespread invasive tree that negatively 
affects biodiversity. Tetracycline hydrochloride was selected as a model substance, since it is an antibiotic 
widely present in environmental water. Central composite design was employed to simultaneously investigate 
the effects of adsorbate solution pH, ionic strength (KCl concentration), and adsorbent mass on removal 
efficiency of all three adsorbents, and to find optimal conditions for studying adsorption kinetics and equilibrium 
on the most promising adsorbent. The removal efficiency and adsorbed mass were calculated from the HPLC UV determined concentration of tetracycline post-adsorption. 
Under optimal conditions (10.18 mg of adsorbent, pH 4.42, and ionic strength 165mM), AC800 showed the 
highest affinity for tetracycline, i.e. 38.22% removal and adsorbed mass of 56.32 mg g-1 compared to 14.57% 
and 21.48 mg g-1 (BC500) and 18.82% and 27.73 mg g-1 (BC800). Removal efficiency of AC800 was strongly 
influenced by the adsorbent mass and solution pH. The kinetics study showed a rapid adsorption process 
(equilibrium attained in 120 minutes), while equilibrium studies revealed a high adsorption capacity for 
tetracycline (131.55 mg g-1). AC800 has been shown to be a promising novel drug adsorbent and should be 
further tested for its suitability in water treatment and sample preparation.",
publisher = "Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu, Polskie Towarzystwo Farmaceutyczne, Stowarzyszenie Stop Nielegalnym Farmaceutykom",
journal = "IV Poznańska Konferencja  Naukowo – Szkoleniowej, 23-24.10.",
title = "Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5479"
}
Stojanović, J., Zalewski, P., Otašević, B., Zečević, M., Malenović, A., Janošević-Ležaić, A., Ranđelović, D.,& Protić, A.. (2023). Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline. in IV Poznańska Konferencja  Naukowo – Szkoleniowej, 23-24.10.
Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu..
https://hdl.handle.net/21.15107/rcub_farfar_5479
Stojanović J, Zalewski P, Otašević B, Zečević M, Malenović A, Janošević-Ležaić A, Ranđelović D, Protić A. Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline. in IV Poznańska Konferencja  Naukowo – Szkoleniowej, 23-24.10.. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5479 .
Stojanović, Jevrem, Zalewski, P., Otašević, Biljana, Zečević, Mira, Malenović, Anđelija, Janošević-Ležaić, Aleksandra, Ranđelović, D., Protić, Ana, "Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline" in IV Poznańska Konferencja  Naukowo – Szkoleniowej, 23-24.10. (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5479 .

Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination

Rmandić, Milena; Vasilić, Đorđe; Rašević, Marija; Zečević, Mira; Otašević, Biljana; Protić, Ana; Malenović, Anđelija

(MDPI, 2023)

TY  - JOUR
AU  - Rmandić, Milena
AU  - Vasilić, Đorđe
AU  - Rašević, Marija
AU  - Zečević, Mira
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Malenović, Anđelija
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5055
AB  - In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (t_imp. V, t_imp. V − t_imp. I, S and <WUSP>) was studied by Box–Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett–Burman design. P_imp II and P_imp V were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination
VL  - 16
IS  - 9
DO  - 10.3390/ph16091296
ER  - 
@article{
author = "Rmandić, Milena and Vasilić, Đorđe and Rašević, Marija and Zečević, Mira and Otašević, Biljana and Protić, Ana and Malenović, Anđelija",
year = "2023",
abstract = "In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (t_imp. V, t_imp. V − t_imp. I, S and <WUSP>) was studied by Box–Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett–Burman design. P_imp II and P_imp V were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination",
volume = "16",
number = "9",
doi = "10.3390/ph16091296"
}
Rmandić, M., Vasilić, Đ., Rašević, M., Zečević, M., Otašević, B., Protić, A.,& Malenović, A.. (2023). Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination. in Pharmaceuticals
MDPI., 16(9).
https://doi.org/10.3390/ph16091296
Rmandić M, Vasilić Đ, Rašević M, Zečević M, Otašević B, Protić A, Malenović A. Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination. in Pharmaceuticals. 2023;16(9).
doi:10.3390/ph16091296 .
Rmandić, Milena, Vasilić, Đorđe, Rašević, Marija, Zečević, Mira, Otašević, Biljana, Protić, Ana, Malenović, Anđelija, "Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination" in Pharmaceuticals, 16, no. 9 (2023),
https://doi.org/10.3390/ph16091296 . .

Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin

Rašević, Marija; Malenović, Anđelija; Protić, Ana; Zečević, Mira

(Elsevier B.V., 2023)

TY  - JOUR
AU  - Rašević, Marija
AU  - Malenović, Anđelija
AU  - Protić, Ana
AU  - Zečević, Mira
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4981
AB  - In this paper, method for enantiomeric purity testing of fourth-generation fluoroquinolone, moxifloxacin hydrochloride, was developed and validated. Exceptional enantioselectivity for this assay was achieved using cyclodextrin type Chiral Stationary Phase (CSP), phenylcarbamate-β-cyclodextrin CSP, and mobile phase consisted of acetonitrile and triethylammonium acetate (TEAA) buffer. Analytical Quality by Design (AQbD) methodology, comprising Design of Experiments (DoE) - Design Space (DS) approach, was used for method development. In order to select appropriate Critical Method Parameters (CMPs), risk assessment was done using combined three step strategy that involved Ishikawa diagram - CNX (Control, Noise and eXperimental) - FMEA (Failure Mode and Effect Analysis). Three CMPs were further selected and investigated in this study: acetonitrile content in the mobile phase (30–50%, v/v), triethylamine content in the TEAA buffer (0.1–1.5%, v/v) and aqueous phase pH (3.5–4.5). Monte Carlo simulations were performed and 3D-DS was computed. One point situated in the center of 3D-DS was selected as working point for method validation, with the following values of CMPs: acetonitrile content in the mobile phase set to 37% (v/v), triethylamine content in TEAA 0.8% and pH value of the aqueous phase set at 4.0. Also, 2D-DS was created (with fixed one factor – pH value of aqueous phase at 4.0) which also gave us confirmation that the selection of working conditions was suitable. The proposed enantioselective method was further on tested for its quantitative robustness, as well as for its suitability for the intended purpose through validation studies.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin
VL  - 235
DO  - 10.1016/j.jpba.2023.115645
ER  - 
@article{
author = "Rašević, Marija and Malenović, Anđelija and Protić, Ana and Zečević, Mira",
year = "2023",
abstract = "In this paper, method for enantiomeric purity testing of fourth-generation fluoroquinolone, moxifloxacin hydrochloride, was developed and validated. Exceptional enantioselectivity for this assay was achieved using cyclodextrin type Chiral Stationary Phase (CSP), phenylcarbamate-β-cyclodextrin CSP, and mobile phase consisted of acetonitrile and triethylammonium acetate (TEAA) buffer. Analytical Quality by Design (AQbD) methodology, comprising Design of Experiments (DoE) - Design Space (DS) approach, was used for method development. In order to select appropriate Critical Method Parameters (CMPs), risk assessment was done using combined three step strategy that involved Ishikawa diagram - CNX (Control, Noise and eXperimental) - FMEA (Failure Mode and Effect Analysis). Three CMPs were further selected and investigated in this study: acetonitrile content in the mobile phase (30–50%, v/v), triethylamine content in the TEAA buffer (0.1–1.5%, v/v) and aqueous phase pH (3.5–4.5). Monte Carlo simulations were performed and 3D-DS was computed. One point situated in the center of 3D-DS was selected as working point for method validation, with the following values of CMPs: acetonitrile content in the mobile phase set to 37% (v/v), triethylamine content in TEAA 0.8% and pH value of the aqueous phase set at 4.0. Also, 2D-DS was created (with fixed one factor – pH value of aqueous phase at 4.0) which also gave us confirmation that the selection of working conditions was suitable. The proposed enantioselective method was further on tested for its quantitative robustness, as well as for its suitability for the intended purpose through validation studies.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin",
volume = "235",
doi = "10.1016/j.jpba.2023.115645"
}
Rašević, M., Malenović, A., Protić, A.,& Zečević, M.. (2023). Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 235.
https://doi.org/10.1016/j.jpba.2023.115645
Rašević M, Malenović A, Protić A, Zečević M. Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin. in Journal of Pharmaceutical and Biomedical Analysis. 2023;235.
doi:10.1016/j.jpba.2023.115645 .
Rašević, Marija, Malenović, Anđelija, Protić, Ana, Zečević, Mira, "Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin" in Journal of Pharmaceutical and Biomedical Analysis, 235 (2023),
https://doi.org/10.1016/j.jpba.2023.115645 . .

Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids

Walther, Rasmus; Krmar, Jovana; Leistner, Adrian; Svrkota, Bojana; Otašević, Biljana; Malenović, Anđelija; Holzgrabe, Ulrike; Protić, Ana

(MDPI, 2023)

TY  - JOUR
AU  - Walther, Rasmus
AU  - Krmar, Jovana
AU  - Leistner, Adrian
AU  - Svrkota, Bojana
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Holzgrabe, Ulrike
AU  - Protić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4698
AB  - An alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs) is urgently needed. The objective was therefore to propose a robust liquid chromatography method with charged aerosol detection for the analysis of polysorbate 80 (PS80) and magnesium stearate. FAs with different numbers of carbon atoms in the chain necessitated the use of a gradient method with a Hypersil Gold C18 column and acetonitrile as organic modifier. The risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR). Formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate were identified as critical method parameters (CMPs). The initial and final percentages of acetonitrile were fixed while the remaining CMPs were fine-tuned using response surface methodology. Critical method attributes included the baseline separation of adjacent peaks (α-linolenic and myristic acid, and oleic and petroselinic acid) and the retention factor of the last compound eluted, stearic acid. The MODR was calculated by Monte Carlo simulations with a probability equal or greater than 90%. Finally, the column temperature was set at 33 °C, the flow rate was 0.575 mL/min, and acetonitrile linearly increased from 70 to 80% (v/v) within 14.2 min.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids
VL  - 16
IS  - 4
DO  - 10.3390/ph16040478
ER  - 
@article{
author = "Walther, Rasmus and Krmar, Jovana and Leistner, Adrian and Svrkota, Bojana and Otašević, Biljana and Malenović, Anđelija and Holzgrabe, Ulrike and Protić, Ana",
year = "2023",
abstract = "An alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs) is urgently needed. The objective was therefore to propose a robust liquid chromatography method with charged aerosol detection for the analysis of polysorbate 80 (PS80) and magnesium stearate. FAs with different numbers of carbon atoms in the chain necessitated the use of a gradient method with a Hypersil Gold C18 column and acetonitrile as organic modifier. The risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR). Formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate were identified as critical method parameters (CMPs). The initial and final percentages of acetonitrile were fixed while the remaining CMPs were fine-tuned using response surface methodology. Critical method attributes included the baseline separation of adjacent peaks (α-linolenic and myristic acid, and oleic and petroselinic acid) and the retention factor of the last compound eluted, stearic acid. The MODR was calculated by Monte Carlo simulations with a probability equal or greater than 90%. Finally, the column temperature was set at 33 °C, the flow rate was 0.575 mL/min, and acetonitrile linearly increased from 70 to 80% (v/v) within 14.2 min.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids",
volume = "16",
number = "4",
doi = "10.3390/ph16040478"
}
Walther, R., Krmar, J., Leistner, A., Svrkota, B., Otašević, B., Malenović, A., Holzgrabe, U.,& Protić, A.. (2023). Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids. in Pharmaceuticals
MDPI., 16(4).
https://doi.org/10.3390/ph16040478
Walther R, Krmar J, Leistner A, Svrkota B, Otašević B, Malenović A, Holzgrabe U, Protić A. Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids. in Pharmaceuticals. 2023;16(4).
doi:10.3390/ph16040478 .
Walther, Rasmus, Krmar, Jovana, Leistner, Adrian, Svrkota, Bojana, Otašević, Biljana, Malenović, Anđelija, Holzgrabe, Ulrike, Protić, Ana, "Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids" in Pharmaceuticals, 16, no. 4 (2023),
https://doi.org/10.3390/ph16040478 . .
1

Baseline Correction for HPLC Chromatograms by Using Free Open-Source Software

Gkountanas, Kostas; Dagla, Ioanna; Gikas, Evangelos; Malenović, Anđelija; Dotsikas, Yannis

(MDPI, 2023)

TY  - JOUR
AU  - Gkountanas, Kostas
AU  - Dagla, Ioanna
AU  - Gikas, Evangelos
AU  - Malenović, Anđelija
AU  - Dotsikas, Yannis
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4998
AB  - Chromatograms with overlapping peaks and a baseline rise or upset constitute a great challenge for analysts. Such a case regarding the analysis of bupropion hydrochloride and its 5 impurities in a tablet formulation was used as a model. A baseline correction technique for liquid chromatography coupled with diode array detection is described by using Rstudio. The asymmetry least squares (ALS) algorithm was used as implemented in the “baseline” package, with parameters lambda and p set to 4 and 0.05, respectively. Peak deconvolution and subsequent integration and area quantification were accomplished through Fytik software. Chromatographic data from the validation procedure were utilized to demonstrate the feasibility of the suggested method and whether this correction affects the outcome of the validation study. Finally, a robustness study was carried out in order to shed light on the factors that have a more significant influence on the baseline correction, showing the reliability of this procedure through random changes in its parameters.
PB  - MDPI
T2  - Analytica
T1  - Baseline Correction for HPLC Chromatograms by Using Free
Open-Source Software
VL  - 4
IS  - 1
SP  - 45
EP  - 53
DO  - 10.3390/analytica4010005
ER  - 
@article{
author = "Gkountanas, Kostas and Dagla, Ioanna and Gikas, Evangelos and Malenović, Anđelija and Dotsikas, Yannis",
year = "2023",
abstract = "Chromatograms with overlapping peaks and a baseline rise or upset constitute a great challenge for analysts. Such a case regarding the analysis of bupropion hydrochloride and its 5 impurities in a tablet formulation was used as a model. A baseline correction technique for liquid chromatography coupled with diode array detection is described by using Rstudio. The asymmetry least squares (ALS) algorithm was used as implemented in the “baseline” package, with parameters lambda and p set to 4 and 0.05, respectively. Peak deconvolution and subsequent integration and area quantification were accomplished through Fytik software. Chromatographic data from the validation procedure were utilized to demonstrate the feasibility of the suggested method and whether this correction affects the outcome of the validation study. Finally, a robustness study was carried out in order to shed light on the factors that have a more significant influence on the baseline correction, showing the reliability of this procedure through random changes in its parameters.",
publisher = "MDPI",
journal = "Analytica",
title = "Baseline Correction for HPLC Chromatograms by Using Free
Open-Source Software",
volume = "4",
number = "1",
pages = "45-53",
doi = "10.3390/analytica4010005"
}
Gkountanas, K., Dagla, I., Gikas, E., Malenović, A.,& Dotsikas, Y.. (2023). Baseline Correction for HPLC Chromatograms by Using Free
Open-Source Software. in Analytica
MDPI., 4(1), 45-53.
https://doi.org/10.3390/analytica4010005
Gkountanas K, Dagla I, Gikas E, Malenović A, Dotsikas Y. Baseline Correction for HPLC Chromatograms by Using Free
Open-Source Software. in Analytica. 2023;4(1):45-53.
doi:10.3390/analytica4010005 .
Gkountanas, Kostas, Dagla, Ioanna, Gikas, Evangelos, Malenović, Anđelija, Dotsikas, Yannis, "Baseline Correction for HPLC Chromatograms by Using Free
Open-Source Software" in Analytica, 4, no. 1 (2023):45-53,
https://doi.org/10.3390/analytica4010005 . .

Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment

Martić, Radava; Kotur-Stevuljević, Jelena; Malenović, Anđelija; Ušjak, Ljuboš; Petrović, Silvana; Čalija, Bojan; Milić, Jela; Krajišnik, Danina

(SAGE Publications Inc., 2022)

TY  - JOUR
AU  - Martić, Radava
AU  - Kotur-Stevuljević, Jelena
AU  - Malenović, Anđelija
AU  - Ušjak, Ljuboš
AU  - Petrović, Silvana
AU  - Čalija, Bojan
AU  - Milić, Jela
AU  - Krajišnik, Danina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4200
AB  - Fast inverted, oil-in-water (o/w) emulsions, also known as SWitch-Oil-Phase (SWOP) emulsions, express the performances of both o/w and water-in-oil (w/o) emulsions during application to the skin, favoring their use as cosmetic carriers in sunscreen products. The objective of this study was to investigate the antioxidant potential (by 2 different methods) and the ultraviolet (UV) absorption ability of SWOP emulsion (S) with incorporated plant-based antioxidants dihydroquercetin (DHQ) and β-carotene (βC), using quercetin (Q) in a reference emulsion, in addition to the evaluation of their physicochemical properties and stability. A new biochemical extra- cellular model for in vitro assessment of antioxidative properties for the SWOP emulsions (S, SQ, SDHQ, and SDHQβC) was developed and compared with the results of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The analyses were performed at 20 °C and 37 °C, and oxidative stress parameters were monitored and statistically analyzed. The sun protection factor (SPF) of the samples was determined in vitro. Q and DHQ incorporated into the SWOP emulsion exhibited a strong DPPH radical scavenging ability. Neither incorporated nor pure βC showed DPPH radical scavenging ability at the tested concentrations. Contrary to that, in the bioenvironment conditions, SDHQβC showed minor antioxidative effects increase and also a significant decrease in exogenous pro-oxidative effects, caused by pro-oxidant, when compared to SDHQ. The obtained SPFs of SDHQβC, SDHQ, and SQ were 5.19, 4.65, and 3.35, respectively. The phys- icochemical stability of the emulsions was satisfactory during 1 month storage. The presented results demonstrated that the SWOP emul- sion is a suitable carrier for antioxidants with a photoprotective ability. The novel biochemical approach could be used in addition to DPPH assay with several advantages, relevant for the testing of antioxidant activity of potential active ingredients in cosmetic products.
PB  - SAGE Publications Inc.
T2  - Natural Product Communications
T1  - Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment
VL  - 17
IS  - 7
DO  - 10.1177/1934578X221112811
ER  - 
@article{
author = "Martić, Radava and Kotur-Stevuljević, Jelena and Malenović, Anđelija and Ušjak, Ljuboš and Petrović, Silvana and Čalija, Bojan and Milić, Jela and Krajišnik, Danina",
year = "2022",
abstract = "Fast inverted, oil-in-water (o/w) emulsions, also known as SWitch-Oil-Phase (SWOP) emulsions, express the performances of both o/w and water-in-oil (w/o) emulsions during application to the skin, favoring their use as cosmetic carriers in sunscreen products. The objective of this study was to investigate the antioxidant potential (by 2 different methods) and the ultraviolet (UV) absorption ability of SWOP emulsion (S) with incorporated plant-based antioxidants dihydroquercetin (DHQ) and β-carotene (βC), using quercetin (Q) in a reference emulsion, in addition to the evaluation of their physicochemical properties and stability. A new biochemical extra- cellular model for in vitro assessment of antioxidative properties for the SWOP emulsions (S, SQ, SDHQ, and SDHQβC) was developed and compared with the results of 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The analyses were performed at 20 °C and 37 °C, and oxidative stress parameters were monitored and statistically analyzed. The sun protection factor (SPF) of the samples was determined in vitro. Q and DHQ incorporated into the SWOP emulsion exhibited a strong DPPH radical scavenging ability. Neither incorporated nor pure βC showed DPPH radical scavenging ability at the tested concentrations. Contrary to that, in the bioenvironment conditions, SDHQβC showed minor antioxidative effects increase and also a significant decrease in exogenous pro-oxidative effects, caused by pro-oxidant, when compared to SDHQ. The obtained SPFs of SDHQβC, SDHQ, and SQ were 5.19, 4.65, and 3.35, respectively. The phys- icochemical stability of the emulsions was satisfactory during 1 month storage. The presented results demonstrated that the SWOP emul- sion is a suitable carrier for antioxidants with a photoprotective ability. The novel biochemical approach could be used in addition to DPPH assay with several advantages, relevant for the testing of antioxidant activity of potential active ingredients in cosmetic products.",
publisher = "SAGE Publications Inc.",
journal = "Natural Product Communications",
title = "Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment",
volume = "17",
number = "7",
doi = "10.1177/1934578X221112811"
}
Martić, R., Kotur-Stevuljević, J., Malenović, A., Ušjak, L., Petrović, S., Čalija, B., Milić, J.,& Krajišnik, D.. (2022). Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment. in Natural Product Communications
SAGE Publications Inc.., 17(7).
https://doi.org/10.1177/1934578X221112811
Martić R, Kotur-Stevuljević J, Malenović A, Ušjak L, Petrović S, Čalija B, Milić J, Krajišnik D. Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment. in Natural Product Communications. 2022;17(7).
doi:10.1177/1934578X221112811 .
Martić, Radava, Kotur-Stevuljević, Jelena, Malenović, Anđelija, Ušjak, Ljuboš, Petrović, Silvana, Čalija, Bojan, Milić, Jela, Krajišnik, Danina, "Fast Inverted Photoprotective o/w Emulsions Loaded With Dihydroquercetin and β-Carotene: An Innovative Approach to In Vitro Assessment of Antioxidant Activity in a Bioenvironment" in Natural Product Communications, 17, no. 7 (2022),
https://doi.org/10.1177/1934578X221112811 . .

Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents

Dabetić, Nevena; Todorović, Vanja; Malenović, Anđelija; Šobajić, Slađana; Marković, Bojan

(MDPI, 2022)

TY  - JOUR
AU  - Dabetić, Nevena
AU  - Todorović, Vanja
AU  - Malenović, Anđelija
AU  - Šobajić, Slađana
AU  - Marković, Bojan
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4268
AB  - Winemaking generates large quantities of grape waste consisting of seeds, skin and stalks. Given that grape seeds are a rich source of different bioactive compounds, the main goal of this research was to optimize grape seed phenol extraction using a Box–Behnken design. The following conditions were derived from the optimization process: sample:solvent ratio of 1:10 w/v, extraction time of 30 min and extraction temperature of 50 °C. In addition, a sustainable (green) approach for obtaining extracts was developed by comparing choline chloride:citric acid-ChCit (natural deep eutectic solvent (NADES)) and ethanol extraction methods with respect to phenol profiles and antioxidant activity. This study was conducted on seeds from eight different red grape varieties. Phenolic acids, flavan-3-ols and procyanidins were characterized using HPLC–MS/MS, and the concentration of procyanidin B1 was above 1 mg/g of dry weight in all analyzed samples. The contents of all phenol classes and antioxidant activities were found to not differ significantly between the solvents, but NADES was found to offer valuable advantages. Importantly, ChCit showed a strong affinity toward procyanidins and a strong correlation between antioxidant activity and quantified phenolic compounds.
PB  - MDPI
T2  - Antioxidants
T1  - Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents
VL  - 11
IS  - 8
DO  - 10.3390/antiox11081595
ER  - 
@article{
author = "Dabetić, Nevena and Todorović, Vanja and Malenović, Anđelija and Šobajić, Slađana and Marković, Bojan",
year = "2022",
abstract = "Winemaking generates large quantities of grape waste consisting of seeds, skin and stalks. Given that grape seeds are a rich source of different bioactive compounds, the main goal of this research was to optimize grape seed phenol extraction using a Box–Behnken design. The following conditions were derived from the optimization process: sample:solvent ratio of 1:10 w/v, extraction time of 30 min and extraction temperature of 50 °C. In addition, a sustainable (green) approach for obtaining extracts was developed by comparing choline chloride:citric acid-ChCit (natural deep eutectic solvent (NADES)) and ethanol extraction methods with respect to phenol profiles and antioxidant activity. This study was conducted on seeds from eight different red grape varieties. Phenolic acids, flavan-3-ols and procyanidins were characterized using HPLC–MS/MS, and the concentration of procyanidin B1 was above 1 mg/g of dry weight in all analyzed samples. The contents of all phenol classes and antioxidant activities were found to not differ significantly between the solvents, but NADES was found to offer valuable advantages. Importantly, ChCit showed a strong affinity toward procyanidins and a strong correlation between antioxidant activity and quantified phenolic compounds.",
publisher = "MDPI",
journal = "Antioxidants",
title = "Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents",
volume = "11",
number = "8",
doi = "10.3390/antiox11081595"
}
Dabetić, N., Todorović, V., Malenović, A., Šobajić, S.,& Marković, B.. (2022). Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents. in Antioxidants
MDPI., 11(8).
https://doi.org/10.3390/antiox11081595
Dabetić N, Todorović V, Malenović A, Šobajić S, Marković B. Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents. in Antioxidants. 2022;11(8).
doi:10.3390/antiox11081595 .
Dabetić, Nevena, Todorović, Vanja, Malenović, Anđelija, Šobajić, Slađana, Marković, Bojan, "Optimization of Extraction and HPLC–MS/MS Profiling of Phenolic Compounds from Red Grape Seed Extracts Using Conventional and Deep Eutectic Solvents" in Antioxidants, 11, no. 8 (2022),
https://doi.org/10.3390/antiox11081595 . .
5
6

Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin

Ćirić, Ana; Milinković Budinčić, Jelena; Dobričić, Vladimir; Rmandić, Milena; Barudžija, Tanja; Malenović, Anđelija; Petrović, Lidija; Đekić, Ljiljana

(Elsevier B.V., 2022)

TY  - JOUR
AU  - Ćirić, Ana
AU  - Milinković Budinčić, Jelena
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Petrović, Lidija
AU  - Đekić, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4272
AB  - Escin is an amphiphilic and weakly acidic drug that oral administration may lead to the irritation of gastric mucosa. The entrapment of escin into chitosan (CH)/xanthan gum (XG)-based polyelectrolyte complexes (PECs) can facilitate controlled drug release which may be beneficial for the reduction of its side effects. This study aimed to investigate the influence of escin content and drying method on the formation, physicochemical, and controlled, pH-dependent drug release properties of CH/XG-based PECs. Measurements of transmittance, con- ductivity, and rheological characterization confirmed the formation of CH/XG-based PECs with escin entrapped at escin-to-polymers mass ratios 1:1, 1:2, and 1:4. Ambient-dried PECs had higher yield, entrapment efficiency, and escin content in comparison with spray-dried ones. FT-IR spectra confirmed the interactions between CH, XG, and escin, which were stronger in ambient-dried PECs. PXRD and DSC analyses showed the amorphous escin character in all dry PECs, regardless of the drying method. The most promising controlled and pH-dependent in vitro escin release was from the ambient-dried PEC at the escin-to-polymers mass ratio of 1:1. For that reason and due to the highest yield and entrapment efficiency, this carrier has the potential to prevent the irritation of gastric mucosa after oral administration of escin.
PB  - Elsevier B.V.
T2  - International Journal of Biological Macromolecules
T1  - Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin
VL  - 221
SP  - 48
EP  - 60
DO  - 10.1016/j.ijbiomac.2022.08.190
ER  - 
@article{
author = "Ćirić, Ana and Milinković Budinčić, Jelena and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Petrović, Lidija and Đekić, Ljiljana",
year = "2022",
abstract = "Escin is an amphiphilic and weakly acidic drug that oral administration may lead to the irritation of gastric mucosa. The entrapment of escin into chitosan (CH)/xanthan gum (XG)-based polyelectrolyte complexes (PECs) can facilitate controlled drug release which may be beneficial for the reduction of its side effects. This study aimed to investigate the influence of escin content and drying method on the formation, physicochemical, and controlled, pH-dependent drug release properties of CH/XG-based PECs. Measurements of transmittance, con- ductivity, and rheological characterization confirmed the formation of CH/XG-based PECs with escin entrapped at escin-to-polymers mass ratios 1:1, 1:2, and 1:4. Ambient-dried PECs had higher yield, entrapment efficiency, and escin content in comparison with spray-dried ones. FT-IR spectra confirmed the interactions between CH, XG, and escin, which were stronger in ambient-dried PECs. PXRD and DSC analyses showed the amorphous escin character in all dry PECs, regardless of the drying method. The most promising controlled and pH-dependent in vitro escin release was from the ambient-dried PEC at the escin-to-polymers mass ratio of 1:1. For that reason and due to the highest yield and entrapment efficiency, this carrier has the potential to prevent the irritation of gastric mucosa after oral administration of escin.",
publisher = "Elsevier B.V.",
journal = "International Journal of Biological Macromolecules",
title = "Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin",
volume = "221",
pages = "48-60",
doi = "10.1016/j.ijbiomac.2022.08.190"
}
Ćirić, A., Milinković Budinčić, J., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A., Petrović, L.,& Đekić, L.. (2022). Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin. in International Journal of Biological Macromolecules
Elsevier B.V.., 221, 48-60.
https://doi.org/10.1016/j.ijbiomac.2022.08.190
Ćirić A, Milinković Budinčić J, Dobričić V, Rmandić M, Barudžija T, Malenović A, Petrović L, Đekić L. Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin. in International Journal of Biological Macromolecules. 2022;221:48-60.
doi:10.1016/j.ijbiomac.2022.08.190 .
Ćirić, Ana, Milinković Budinčić, Jelena, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Petrović, Lidija, Đekić, Ljiljana, "Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin" in International Journal of Biological Macromolecules, 221 (2022):48-60,
https://doi.org/10.1016/j.ijbiomac.2022.08.190 . .
5
4

Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen

Ćirić, Ana; Milinković Budinčić, Jelena; Medarević, Đorđe; Dobričić, Vladimir; Rmandić, Milena; Barudžija, Tanja; Malenović, Anđelija; Petrović, Lidija; Đekić, Ljiljana

(Savez farmaceutskih udruženja Srbije, 2022)

TY  - JOUR
AU  - Ćirić, Ana
AU  - Milinković Budinčić, Jelena
AU  - Medarević, Đorđe
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Petrović, Lidija
AU  - Đekić, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4179
AB  - Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to
enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation
of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical
and biopharmaceutical properties. The aim of this study was to investigate the effect of spray-
drying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug
release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs
which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency,
and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs.
Better flowability of spray-dried PECs was attributed to the almost spherical particle shape,
shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization
of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient
conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric
acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was
controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried
PECs provided better control of ibuprofen diffusion from the carrier compared to the ambient-
dried ones.
AB  - Polielektrolitni kompleksi (PEK) su atraktivni nosači sa potencijalom poboljšanja peroralne isporuke slabo rastvorljivih visokodoziranih lekovitih supstanci niske molekulske mase. Formulisanje čvrstih oralnih farmaceutskih oblika na bazi PEK zahteva njihovo sušenje, što može uticati na fizičko-hemijska i biofarmaceutska svojstva kompleksa. Cilj ove studije bio je da se ispita efekat sušenja raspršivanjem na svojstva PEK hitozana i ksantan gume u koje je inkorporiran ibuprofen i da se proceni kinetika oslobađanja lekovite supstance iz takvih PEK napunjenih u tvrde kapsule u poređenju sa odgovarajućim PEK koji su sušeni pod ambijentalnim uslovima. Prinos, sadržaj ibuprofena, efikasnost inkorporiranja i sadržaj vlage PEK sušenih raspršivanjem bili su niži nego kod PEK sušenih pod ambijentalnim uslovima. Bolja protočnost PEK osušenih raspršivanjem je posledica skoro sfernog oblika čestica, što je pokazano skenirajućom elektronskom mikroskopijom. Rezultati DSC i PXRD analiza su potvrdili amorfizaciju ibuprofena tokom sušenja raspršivanjem. Ispitivani PEK osušeni pod različitim uslovima imali su visoku sposobnost rehidratacije u 0,1 M hlorovodoničnoj kiselini (pH 1,2) i fosfatnom puferu pH 7,4. In vitro oslobađanje ibuprofena iz osušenih PEK bilo je kontrolisano tokom 12 h uz oslobađanje približno 30% inkorporiranog ibuprofena. PEK sušeni raspršivanjem obezbedili su bolju kontrolu difuzije ibuprofena iz nosača u poređenju sa onima sušenim pod ambijentalnim uslovima.
PB  - Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen
T1  - Uticaj postupka sušenja raspršivanjem na svojstva polielektrolitnih kompleksa hitozana i ksantan gume kao nosača za peroralnu isporuku ibuprofena
VL  - 72
IS  - 1
SP  - 36
EP  - 60
DO  - 10.5937/arhfarm72-35133
ER  - 
@article{
author = "Ćirić, Ana and Milinković Budinčić, Jelena and Medarević, Đorđe and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Petrović, Lidija and Đekić, Ljiljana",
year = "2022",
abstract = "Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to
enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation
of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical
and biopharmaceutical properties. The aim of this study was to investigate the effect of spray-
drying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug
release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs
which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency,
and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs.
Better flowability of spray-dried PECs was attributed to the almost spherical particle shape,
shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization
of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient
conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric
acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was
controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried
PECs provided better control of ibuprofen diffusion from the carrier compared to the ambient-
dried ones., Polielektrolitni kompleksi (PEK) su atraktivni nosači sa potencijalom poboljšanja peroralne isporuke slabo rastvorljivih visokodoziranih lekovitih supstanci niske molekulske mase. Formulisanje čvrstih oralnih farmaceutskih oblika na bazi PEK zahteva njihovo sušenje, što može uticati na fizičko-hemijska i biofarmaceutska svojstva kompleksa. Cilj ove studije bio je da se ispita efekat sušenja raspršivanjem na svojstva PEK hitozana i ksantan gume u koje je inkorporiran ibuprofen i da se proceni kinetika oslobađanja lekovite supstance iz takvih PEK napunjenih u tvrde kapsule u poređenju sa odgovarajućim PEK koji su sušeni pod ambijentalnim uslovima. Prinos, sadržaj ibuprofena, efikasnost inkorporiranja i sadržaj vlage PEK sušenih raspršivanjem bili su niži nego kod PEK sušenih pod ambijentalnim uslovima. Bolja protočnost PEK osušenih raspršivanjem je posledica skoro sfernog oblika čestica, što je pokazano skenirajućom elektronskom mikroskopijom. Rezultati DSC i PXRD analiza su potvrdili amorfizaciju ibuprofena tokom sušenja raspršivanjem. Ispitivani PEK osušeni pod različitim uslovima imali su visoku sposobnost rehidratacije u 0,1 M hlorovodoničnoj kiselini (pH 1,2) i fosfatnom puferu pH 7,4. In vitro oslobađanje ibuprofena iz osušenih PEK bilo je kontrolisano tokom 12 h uz oslobađanje približno 30% inkorporiranog ibuprofena. PEK sušeni raspršivanjem obezbedili su bolju kontrolu difuzije ibuprofena iz nosača u poređenju sa onima sušenim pod ambijentalnim uslovima.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen, Uticaj postupka sušenja raspršivanjem na svojstva polielektrolitnih kompleksa hitozana i ksantan gume kao nosača za peroralnu isporuku ibuprofena",
volume = "72",
number = "1",
pages = "36-60",
doi = "10.5937/arhfarm72-35133"
}
Ćirić, A., Milinković Budinčić, J., Medarević, Đ., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A., Petrović, L.,& Đekić, L.. (2022). Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 72(1), 36-60.
https://doi.org/10.5937/arhfarm72-35133
Ćirić A, Milinković Budinčić J, Medarević Đ, Dobričić V, Rmandić M, Barudžija T, Malenović A, Petrović L, Đekić L. Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen. in Arhiv za farmaciju. 2022;72(1):36-60.
doi:10.5937/arhfarm72-35133 .
Ćirić, Ana, Milinković Budinčić, Jelena, Medarević, Đorđe, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Petrović, Lidija, Đekić, Ljiljana, "Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen" in Arhiv za farmaciju, 72, no. 1 (2022):36-60,
https://doi.org/10.5937/arhfarm72-35133 . .
3
3

Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia

Vezmar-Kovačević, Sandra; Odalović, Marina; Tadić, Ivana; Vučićević, Katarina; Malenović, Anđelija

(European Association of Faculties of Pharmacy, 2022)

TY  - CONF
AU  - Vezmar-Kovačević, Sandra
AU  - Odalović, Marina
AU  - Tadić, Ivana
AU  - Vučićević, Katarina
AU  - Malenović, Anđelija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4822
AB  - Introduction: At the Faculty of Pharmacy University of Belgrade, the Objective Structured Clinical Examination (0SCE) was introduced to assess clinical competences and communication skills of pharmacy students following their 6-weeks practice in public pharmacies during the 10th semester. Methods: The OSCE consisted of one patient case that was presented to the student firstly in a short written form. The patient case had at least one drug-related problem that the student was expected to identify and solve. A teaching assistant played the role of the patient and a teacher assessed the communication skills and clinical competences during the student's interview with the „patient" using a structured form (checklist). The student had limited time (7 minutes) to identify and solve the drug-related problem(s) and to councel the patient. The use of a Drug register and Pharmacotherapy guide were allowed. Results: One hundred fifty students completed the OSCE so far. The students could achieve O-40 points during the exam, according to their performance. The maximal point score was achieved if the student obtained all relevant information from the patient”, identified and solved the drug-related problem(s) and offered appropriate information. The minimal point score (0) was assigned if the student made an error which could harm the patient. The median result of the OSCE was 28 points (interquatile range 10), while 7 students (4.7%) scored 0-9 points, 12 (8.0%) scored 10-19 points, 68 (45.3%) scored 20-29 points, 58 (38.79%) scored 30-39 points and 5 students (3.3%) scored 40 points. Conclusions: The introduction of the OSCE was successful and enabled the teaching staff to obtain a more accurate knowledge of the students’ clinical competences and communication skills as well as to identify gaps in the competences in skills which need to be improved.
PB  - European Association of Faculties of Pharmacy
C3  - EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
T1  - Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia
SP  - 47
EP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4822
ER  - 
@conference{
author = "Vezmar-Kovačević, Sandra and Odalović, Marina and Tadić, Ivana and Vučićević, Katarina and Malenović, Anđelija",
year = "2022",
abstract = "Introduction: At the Faculty of Pharmacy University of Belgrade, the Objective Structured Clinical Examination (0SCE) was introduced to assess clinical competences and communication skills of pharmacy students following their 6-weeks practice in public pharmacies during the 10th semester. Methods: The OSCE consisted of one patient case that was presented to the student firstly in a short written form. The patient case had at least one drug-related problem that the student was expected to identify and solve. A teaching assistant played the role of the patient and a teacher assessed the communication skills and clinical competences during the student's interview with the „patient" using a structured form (checklist). The student had limited time (7 minutes) to identify and solve the drug-related problem(s) and to councel the patient. The use of a Drug register and Pharmacotherapy guide were allowed. Results: One hundred fifty students completed the OSCE so far. The students could achieve O-40 points during the exam, according to their performance. The maximal point score was achieved if the student obtained all relevant information from the patient”, identified and solved the drug-related problem(s) and offered appropriate information. The minimal point score (0) was assigned if the student made an error which could harm the patient. The median result of the OSCE was 28 points (interquatile range 10), while 7 students (4.7%) scored 0-9 points, 12 (8.0%) scored 10-19 points, 68 (45.3%) scored 20-29 points, 58 (38.79%) scored 30-39 points and 5 students (3.3%) scored 40 points. Conclusions: The introduction of the OSCE was successful and enabled the teaching staff to obtain a more accurate knowledge of the students’ clinical competences and communication skills as well as to identify gaps in the competences in skills which need to be improved.",
publisher = "European Association of Faculties of Pharmacy",
journal = "EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book",
title = "Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia",
pages = "47-47",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4822"
}
Vezmar-Kovačević, S., Odalović, M., Tadić, I., Vučićević, K.,& Malenović, A.. (2022). Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
European Association of Faculties of Pharmacy., 47-47.
https://hdl.handle.net/21.15107/rcub_farfar_4822
Vezmar-Kovačević S, Odalović M, Tadić I, Vučićević K, Malenović A. Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book. 2022;:47-47.
https://hdl.handle.net/21.15107/rcub_farfar_4822 .
Vezmar-Kovačević, Sandra, Odalović, Marina, Tadić, Ivana, Vučićević, Katarina, Malenović, Anđelija, "Introduction of an Objective Structured Clinical Examination for Pharmacy Students in Serbia" in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book (2022):47-47,
https://hdl.handle.net/21.15107/rcub_farfar_4822 .

Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach

Tomić, Jovana; Đajić, Nevena; Agbaba, Danica; Otašević, Biljana; Malenović, Anđelija; Protić, Ana

(Akademiai Kiado ZRt., 2022)

TY  - JOUR
AU  - Tomić, Jovana
AU  - Đajić, Nevena
AU  - Agbaba, Danica
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4331
AB  - This paper is aimed at developing a gradient elution reversed-phase high-performance liquid chromatography (RP-HPLC) method for the separation of a complex mixture composed of ivabradine and its eleven impurities, in a reasonable timeframe. In order to obtain a robust and reliable HPLC method for separation of this mixture, Analytical Quality by Design (AQbD) was applied. This approach demonstrated to be useful in development of a long lasting life cycle methods. Four chromatographic variables were defined as key method parameters (KMPs) and optimized towards the analytical target profile (ATP). Designated KMPs were initial and final amount of acetonitrile in the mobile phase, pH value of the aqueous phase and gradient time, while resolutions of critical peak pairs were denoted as critical method attributes (CMAs). Relationships between KMPs and CMAs were obtained with the aid of Design of Experiments (DoEs) methodology among which Box-Behnken design (BBD) was employed to gain valid mathematical models. Obtained mathematical equations were used to construct the Design Space (DS) and select reliable optimal separation conditions. They included 11% (v/v) and 34% (v/v) of initial and final amount of acetonitrile, respectively, as well as 45 min of gradient elution time and 20 mM ammonium acetate as aqueous mobile phase with pH set to 7.35. The possibility to separate the diastereoisomers of impurity X was also evaluated. It was demonstrated that this separation could not be achieved in gradient elution mode within the defined variable domains and in a reasonable time span. The developed method was validated according to ICH Q2 (R1) guideline and met all the required criteria.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach
VL  - 34
IS  - 1
SP  - 1
EP  - 11
DO  - 10.1556/1326.2021.00885
ER  - 
@article{
author = "Tomić, Jovana and Đajić, Nevena and Agbaba, Danica and Otašević, Biljana and Malenović, Anđelija and Protić, Ana",
year = "2022",
abstract = "This paper is aimed at developing a gradient elution reversed-phase high-performance liquid chromatography (RP-HPLC) method for the separation of a complex mixture composed of ivabradine and its eleven impurities, in a reasonable timeframe. In order to obtain a robust and reliable HPLC method for separation of this mixture, Analytical Quality by Design (AQbD) was applied. This approach demonstrated to be useful in development of a long lasting life cycle methods. Four chromatographic variables were defined as key method parameters (KMPs) and optimized towards the analytical target profile (ATP). Designated KMPs were initial and final amount of acetonitrile in the mobile phase, pH value of the aqueous phase and gradient time, while resolutions of critical peak pairs were denoted as critical method attributes (CMAs). Relationships between KMPs and CMAs were obtained with the aid of Design of Experiments (DoEs) methodology among which Box-Behnken design (BBD) was employed to gain valid mathematical models. Obtained mathematical equations were used to construct the Design Space (DS) and select reliable optimal separation conditions. They included 11% (v/v) and 34% (v/v) of initial and final amount of acetonitrile, respectively, as well as 45 min of gradient elution time and 20 mM ammonium acetate as aqueous mobile phase with pH set to 7.35. The possibility to separate the diastereoisomers of impurity X was also evaluated. It was demonstrated that this separation could not be achieved in gradient elution mode within the defined variable domains and in a reasonable time span. The developed method was validated according to ICH Q2 (R1) guideline and met all the required criteria.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach",
volume = "34",
number = "1",
pages = "1-11",
doi = "10.1556/1326.2021.00885"
}
Tomić, J., Đajić, N., Agbaba, D., Otašević, B., Malenović, A.,& Protić, A.. (2022). Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(1), 1-11.
https://doi.org/10.1556/1326.2021.00885
Tomić J, Đajić N, Agbaba D, Otašević B, Malenović A, Protić A. Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach. in Acta Chromatographica. 2022;34(1):1-11.
doi:10.1556/1326.2021.00885 .
Tomić, Jovana, Đajić, Nevena, Agbaba, Danica, Otašević, Biljana, Malenović, Anđelija, Protić, Ana, "Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach" in Acta Chromatographica, 34, no. 1 (2022):1-11,
https://doi.org/10.1556/1326.2021.00885 . .
4
3

Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development

Gkountanas, Kostas; Malenović, Anđelija; Dotsikas, Yannis

(MDPI, 2022)

TY  - JOUR
AU  - Gkountanas, Kostas
AU  - Malenović, Anđelija
AU  - Dotsikas, Yannis
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4312
AB  - A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development
VL  - 15
IS  - 10
DO  - 10.3390/ph15101196
ER  - 
@article{
author = "Gkountanas, Kostas and Malenović, Anđelija and Dotsikas, Yannis",
year = "2022",
abstract = "A novel chaotropic chromatography method for the quantitative determination of bupropion and its impurities, following analytical quality-by-design (AQbD) principles, is presented. The analytical target profile (ATP) was defined on the basis of the efficient separation and reliable determination of bupropion and its five impurities in tablets. Preliminary experiments revealed the need for the addition of a gradient elution part. A screening fractional factorial experimental design was employed to select the critical method parameters (CMPs) and a Box–Behnken design (BBD) was utilized to investigate their influence on predefined critical method attributes (CMAs). In order to compute the design space (DS), where CMPs meet predefined acceptance limits with a high level of probability (π ≥ 85%), Monte Carlo simulations were performed. The working point selected from the DS corresponded to the following conditions: 37.5% acetonitrile at the start of the gradient program (up to 70% at the end of the gradient program), 45 mM of potassium hexafluorophosphate in the water phase, and the start of the linear gradient step in the gradient program at 10 min. The method was validated according to ICH guidelines and applied to the analysis of Wellbutrin® tablets containing bupropion hydrochloride.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development",
volume = "15",
number = "10",
doi = "10.3390/ph15101196"
}
Gkountanas, K., Malenović, A.,& Dotsikas, Y.. (2022). Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development. in Pharmaceuticals
MDPI., 15(10).
https://doi.org/10.3390/ph15101196
Gkountanas K, Malenović A, Dotsikas Y. Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development. in Pharmaceuticals. 2022;15(10).
doi:10.3390/ph15101196 .
Gkountanas, Kostas, Malenović, Anđelija, Dotsikas, Yannis, "Determination of Bupropion and Its Impurities via a Chaotropic Chromatography Method Following Analytical Quality-by-Design Principles for Method Development" in Pharmaceuticals, 15, no. 10 (2022),
https://doi.org/10.3390/ph15101196 . .
6
4

Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice

Rmandić, Milena; Stajić, Ana; Jančić, Jasna; Samardžić, Janko; Jović, Nebojša; Malenović, Anđelija

(MDPI, 2022)

TY  - JOUR
AU  - Rmandić, Milena
AU  - Stajić, Ana
AU  - Jančić, Jasna
AU  - Samardžić, Janko
AU  - Jović, Nebojša
AU  - Malenović, Anđelija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4262
AB  - In this research, a UHPLC–MS/MS method was developed and validated for the deter-
mination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of
zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by
monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using
Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 μm particle size) column with mobile phase com-
prising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min,
the column temperature was 30 ◦C and the injection volume was 3 μL. Desolvation temperature,
desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart
software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS
areas were determined by the image processing tool. The influence of hematocrit values (20–60%)
on accuracy and precision was evaluated to determine the range within which method for DBSs is
free from Hct or dependency is within acceptable limits. The validated method was applied to the
determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its
suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was
estimated by correlating its DPS and DBS levels.
PB  - MDPI
T2  - Molecules
T1  - Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice
VL  - 27
IS  - 15
DO  - 10.3390/molecules27154899
ER  - 
@article{
author = "Rmandić, Milena and Stajić, Ana and Jančić, Jasna and Samardžić, Janko and Jović, Nebojša and Malenović, Anđelija",
year = "2022",
abstract = "In this research, a UHPLC–MS/MS method was developed and validated for the deter-
mination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of
zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by
monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using
Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 μm particle size) column with mobile phase com-
prising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min,
the column temperature was 30 ◦C and the injection volume was 3 μL. Desolvation temperature,
desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart
software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS
areas were determined by the image processing tool. The influence of hematocrit values (20–60%)
on accuracy and precision was evaluated to determine the range within which method for DBSs is
free from Hct or dependency is within acceptable limits. The validated method was applied to the
determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its
suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was
estimated by correlating its DPS and DBS levels.",
publisher = "MDPI",
journal = "Molecules",
title = "Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice",
volume = "27",
number = "15",
doi = "10.3390/molecules27154899"
}
Rmandić, M., Stajić, A., Jančić, J., Samardžić, J., Jović, N.,& Malenović, A.. (2022). Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice. in Molecules
MDPI., 27(15).
https://doi.org/10.3390/molecules27154899
Rmandić M, Stajić A, Jančić J, Samardžić J, Jović N, Malenović A. Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice. in Molecules. 2022;27(15).
doi:10.3390/molecules27154899 .
Rmandić, Milena, Stajić, Ana, Jančić, Jasna, Samardžić, Janko, Jović, Nebojša, Malenović, Anđelija, "Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice" in Molecules, 27, no. 15 (2022),
https://doi.org/10.3390/molecules27154899 . .
1
3
3

Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer

Milenković, Milan; Rašević, Marija; Otašević, Biljana; Zečević, Mira; Malenović, Anđelija; Protić, Ana

(Elsevier B.V., 2022)

TY  - JOUR
AU  - Milenković, Milan
AU  - Rašević, Marija
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3977
AB  - Nowadays, method development is strongly focused on reducing time needed for method development and execution. This subject specially concerns gradient elution methods regarding the usual need for trouble shooting assistance with uncertain outcome during the method transfer from one laboratory to another. One of the main reasons for this situation is the dwell volume difference between HPLC systems. Therefore, the aim of this study was to propose a novel method development methodology that would integrate the dwell volumes differences in the optimization process. The proposed approach could be quite useful in industry that has insight in HPLC instruments planned to be used during the method life cycle. It was tested on the model mixture consisting of dabigatran etexilate mesylate and its nine impurities by use of perimental design methodology. Three different (U)HPLC instruments with high dwell volume differences were selected to challenge the methodology. Plan of experiments was defined with Plackett-Burman design for screening phase and D-optimal design for optimization phase. Initial and final amount of organic modifier, time of the gradient elution and pH value of the aqueous phase were selected as variables nificant for the gradient programme profile and included in the optimization stage along with dwell volume values. The separation criteria s between critical peak pairs was selected as output for method optimization while indirect modelling together with Monte Carlo simulations enabled selection of optimal and robust chromatographic conditions. They included 24% (v/v) of initial amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient elution run time and pH value equal to 4.9. The proposed method was successfully validated, met all validation criteria and thus proved its utility.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer
VL  - 207
DO  - 10.1016/j.jpba.2021.114367
ER  - 
@article{
author = "Milenković, Milan and Rašević, Marija and Otašević, Biljana and Zečević, Mira and Malenović, Anđelija and Protić, Ana",
year = "2022",
abstract = "Nowadays, method development is strongly focused on reducing time needed for method development and execution. This subject specially concerns gradient elution methods regarding the usual need for trouble shooting assistance with uncertain outcome during the method transfer from one laboratory to another. One of the main reasons for this situation is the dwell volume difference between HPLC systems. Therefore, the aim of this study was to propose a novel method development methodology that would integrate the dwell volumes differences in the optimization process. The proposed approach could be quite useful in industry that has insight in HPLC instruments planned to be used during the method life cycle. It was tested on the model mixture consisting of dabigatran etexilate mesylate and its nine impurities by use of perimental design methodology. Three different (U)HPLC instruments with high dwell volume differences were selected to challenge the methodology. Plan of experiments was defined with Plackett-Burman design for screening phase and D-optimal design for optimization phase. Initial and final amount of organic modifier, time of the gradient elution and pH value of the aqueous phase were selected as variables nificant for the gradient programme profile and included in the optimization stage along with dwell volume values. The separation criteria s between critical peak pairs was selected as output for method optimization while indirect modelling together with Monte Carlo simulations enabled selection of optimal and robust chromatographic conditions. They included 24% (v/v) of initial amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient elution run time and pH value equal to 4.9. The proposed method was successfully validated, met all validation criteria and thus proved its utility.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer",
volume = "207",
doi = "10.1016/j.jpba.2021.114367"
}
Milenković, M., Rašević, M., Otašević, B., Zečević, M., Malenović, A.,& Protić, A.. (2022). Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 207.
https://doi.org/10.1016/j.jpba.2021.114367
Milenković M, Rašević M, Otašević B, Zečević M, Malenović A, Protić A. Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer. in Journal of Pharmaceutical and Biomedical Analysis. 2022;207.
doi:10.1016/j.jpba.2021.114367 .
Milenković, Milan, Rašević, Marija, Otašević, Biljana, Zečević, Mira, Malenović, Anđelija, Protić, Ana, "Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer" in Journal of Pharmaceutical and Biomedical Analysis, 207 (2022),
https://doi.org/10.1016/j.jpba.2021.114367 . .
1

Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography

Đajić, Nevena; Krmar, Jovana; Rmandić, Milena; Rašević, Marija; Otašević, Biljana; Zečević, Mira; Malenović, Anđelija; Protić, Ana

(Elsevier B.V., 2022)

TY  - JOUR
AU  - Đajić, Nevena
AU  - Krmar, Jovana
AU  - Rmandić, Milena
AU  - Rašević, Marija
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4995
AB  - Most commonly used analytical technique for determination of active pharmaceutical ingredients and their impurities in quality control throughout all phases of drug research, development and manufacture is definitely reversed-phase high performance liquid chromatography (RP-HPLC). However, pharmaceutical industry professionals are often faced with various challenges in RP mode, which cannot be resolved with common variations in the composition of the mobile phase. These challenges often occur when analyzing compounds that contain basic ionizable groups, possess large differences in polarities and require consumption of high amounts of toxic organic solvents. Among available strategies for addressing the aforementioned issues, the most convenient one includes RP-HPLC mobile phase modifications by an addition of the proper chemical compounds. In that respect, RP-HPLC method can be easily adapted to the needs of the analysis without time-consuming and expensive equipment procurement. In this review the chaotropic chromatography, micellar liquid chromatography, and cyclodextrin modified RP-HPLC systems are presented and discussed in details. Special attention is devoted to the theoretical background, the possibility of retention modeling and applications in various fields of pharmacy, as well as their prospective in further research.
PB  - Elsevier B.V.
T2  - Journal of Chromatography Open
T1  - Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography
VL  - 2
DO  - 10.1016/j.jcoa.2021.100023
ER  - 
@article{
author = "Đajić, Nevena and Krmar, Jovana and Rmandić, Milena and Rašević, Marija and Otašević, Biljana and Zečević, Mira and Malenović, Anđelija and Protić, Ana",
year = "2022",
abstract = "Most commonly used analytical technique for determination of active pharmaceutical ingredients and their impurities in quality control throughout all phases of drug research, development and manufacture is definitely reversed-phase high performance liquid chromatography (RP-HPLC). However, pharmaceutical industry professionals are often faced with various challenges in RP mode, which cannot be resolved with common variations in the composition of the mobile phase. These challenges often occur when analyzing compounds that contain basic ionizable groups, possess large differences in polarities and require consumption of high amounts of toxic organic solvents. Among available strategies for addressing the aforementioned issues, the most convenient one includes RP-HPLC mobile phase modifications by an addition of the proper chemical compounds. In that respect, RP-HPLC method can be easily adapted to the needs of the analysis without time-consuming and expensive equipment procurement. In this review the chaotropic chromatography, micellar liquid chromatography, and cyclodextrin modified RP-HPLC systems are presented and discussed in details. Special attention is devoted to the theoretical background, the possibility of retention modeling and applications in various fields of pharmacy, as well as their prospective in further research.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography Open",
title = "Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography",
volume = "2",
doi = "10.1016/j.jcoa.2021.100023"
}
Đajić, N., Krmar, J., Rmandić, M., Rašević, M., Otašević, B., Zečević, M., Malenović, A.,& Protić, A.. (2022). Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography. in Journal of Chromatography Open
Elsevier B.V.., 2.
https://doi.org/10.1016/j.jcoa.2021.100023
Đajić N, Krmar J, Rmandić M, Rašević M, Otašević B, Zečević M, Malenović A, Protić A. Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography. in Journal of Chromatography Open. 2022;2.
doi:10.1016/j.jcoa.2021.100023 .
Đajić, Nevena, Krmar, Jovana, Rmandić, Milena, Rašević, Marija, Otašević, Biljana, Zečević, Mira, Malenović, Anđelija, Protić, Ana, "Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography" in Journal of Chromatography Open, 2 (2022),
https://doi.org/10.1016/j.jcoa.2021.100023 . .
8
8

Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade

Malenović, Anđelija; Kovačević, Milena; Ivanović, Nevena; Protić, Ana; Parojčić, Jelena

(European Association of Faculties of Pharmacy, 2022)

TY  - CONF
AU  - Malenović, Anđelija
AU  - Kovačević, Milena
AU  - Ivanović, Nevena
AU  - Protić, Ana
AU  - Parojčić, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4381
AB  - Introduction: Synchronous lectures tend to be used as the
prevalent method of online instruction, irrespective of
notable differences and obvious limitations when compared
to their in-person delivery. Study aim was to assess students’
perspective on online lectures held during the emergency
remote teaching (ERT) shift due to the COVID-19 pandemic.
Method: Students were invited to take part in online survey
related to their experience with ERT. Survey included 25 items
related to: satisfaction (14 items), motivation (three items),
interaction with peers and lecturers (four items), and
perceived challenges (four items). A 5-point Likert scale was
employed. Statistical analysis was performed using the SPSS
software.
Results: A total of 387 students participated in the survey.
The majority of respondents (79.3%) were junior students.
Among the respondents, 72.6% reported no previous
experience with online learning. Although a relatively high
level of satisfaction was reported (mean score 3.91 ± 0.75),
challenges were also scored relatively high (3.05 ± 0.99),
while interaction was scored somewhat lower (2.98 ± 0.73),
and the lowest mean score was observed for motivation (2.73
± 0.58). Students reported having trouble maintaining
motivation, concentration and focus during online lectures,
which usually took many hours per day. Interaction with
peers was reported as unsatisfactory (2.48 ± 1.46), whereas it
was more feasible with lecturers (3.24 ± 1.42). Students were
quite satisfied with the ability to organise their time flexibly
(71.4%), and with the workload (54.5%), while they were less
convinced that online sessions provided enough
opportunities to reflect on what was learnt (50.1% agree,
25.1% neither agree nor disagree).
Conclusions: The results obtained indicate that students are
somewhat hesitant with respect to online lectures as the
main mode of instruction. Lectures, generally, place students
in a passive role, which is further increased in online delivery.
In order to support students’ engagement and success, online
lectures should be combined with more active instructional
strategies.
PB  - European Association of Faculties of Pharmacy
PB  - International Pharmaceutical Federation (FIP)
C3  - Pharmacy Education
T1  - Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade
VL  - 22
IS  - 3
SP  - 8
EP  - 8
DO  - 10.46542/pe.2022.223.135
ER  - 
@conference{
author = "Malenović, Anđelija and Kovačević, Milena and Ivanović, Nevena and Protić, Ana and Parojčić, Jelena",
year = "2022",
abstract = "Introduction: Synchronous lectures tend to be used as the
prevalent method of online instruction, irrespective of
notable differences and obvious limitations when compared
to their in-person delivery. Study aim was to assess students’
perspective on online lectures held during the emergency
remote teaching (ERT) shift due to the COVID-19 pandemic.
Method: Students were invited to take part in online survey
related to their experience with ERT. Survey included 25 items
related to: satisfaction (14 items), motivation (three items),
interaction with peers and lecturers (four items), and
perceived challenges (four items). A 5-point Likert scale was
employed. Statistical analysis was performed using the SPSS
software.
Results: A total of 387 students participated in the survey.
The majority of respondents (79.3%) were junior students.
Among the respondents, 72.6% reported no previous
experience with online learning. Although a relatively high
level of satisfaction was reported (mean score 3.91 ± 0.75),
challenges were also scored relatively high (3.05 ± 0.99),
while interaction was scored somewhat lower (2.98 ± 0.73),
and the lowest mean score was observed for motivation (2.73
± 0.58). Students reported having trouble maintaining
motivation, concentration and focus during online lectures,
which usually took many hours per day. Interaction with
peers was reported as unsatisfactory (2.48 ± 1.46), whereas it
was more feasible with lecturers (3.24 ± 1.42). Students were
quite satisfied with the ability to organise their time flexibly
(71.4%), and with the workload (54.5%), while they were less
convinced that online sessions provided enough
opportunities to reflect on what was learnt (50.1% agree,
25.1% neither agree nor disagree).
Conclusions: The results obtained indicate that students are
somewhat hesitant with respect to online lectures as the
main mode of instruction. Lectures, generally, place students
in a passive role, which is further increased in online delivery.
In order to support students’ engagement and success, online
lectures should be combined with more active instructional
strategies.",
publisher = "European Association of Faculties of Pharmacy, International Pharmaceutical Federation (FIP)",
journal = "Pharmacy Education",
title = "Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade",
volume = "22",
number = "3",
pages = "8-8",
doi = "10.46542/pe.2022.223.135"
}
Malenović, A., Kovačević, M., Ivanović, N., Protić, A.,& Parojčić, J.. (2022). Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade. in Pharmacy Education
European Association of Faculties of Pharmacy., 22(3), 8-8.
https://doi.org/10.46542/pe.2022.223.135
Malenović A, Kovačević M, Ivanović N, Protić A, Parojčić J. Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade. in Pharmacy Education. 2022;22(3):8-8.
doi:10.46542/pe.2022.223.135 .
Malenović, Anđelija, Kovačević, Milena, Ivanović, Nevena, Protić, Ana, Parojčić, Jelena, "Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade" in Pharmacy Education, 22, no. 3 (2022):8-8,
https://doi.org/10.46542/pe.2022.223.135 . .
1

Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.

Malenović, Anđelija; Kovačević, Milena; Ivanović, Nevena; Protić, Ana; Parojčić, Jelena

(European Association of Faculties of Pharmacy, 2022)

TY  - CONF
AU  - Malenović, Anđelija
AU  - Kovačević, Milena
AU  - Ivanović, Nevena
AU  - Protić, Ana
AU  - Parojčić, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4375
AB  - Synchronous lectures tend to be used as the prevalent
method of online instruction, irrespective of notable differences
and obvious limitations when compared to their in-person delivery.
Study aim was to assess students’ perspective on online lectures
held during the emergency remote teaching (ERT) due to COVID-19
pandemic.
Method: Students were invited to take part in online survey related
to their experience with ERT. Survey included 25 items related to:
satisfaction (14 items), motivation (3 items), interaction with peers
and lecturers (4 items), and perceived challenges (4 items). A 5-point
Likert scale was employed. Statistical analysis was performed using
the SPSS software.
Results: A total of 387 students participated in the survey. Majority
of respondents (79.3%) were junior students. Among them, 72.6%
reported no previous experience with online learning. Although
relatively high level of satisfaction was reported (mean score
3.91±0.75), challenges were also scored relatively high (3.05±0.99),
while interaction was scored somewhat lower (2.98±0.73), and the
least mean score was observed for motivation (2.73±0.58). Students
reported having trouble to keep motivation, concentration and
focus during online lectures, which usually took long hours per day.
Interaction with peers was reported as unsatisfactory (2.48±1.46),
whereas it was more feasible with lecturers (3.24±1.42). Students
were quite satisfied with the possibility to organize their time flexibly
(71.4%), and with respect to the workload (54.5%), while they were
less convinced that online sessions provide enough opportunities
to reflect on what has been learnt (50,1% agree, 25,1% neither
agree nor disagree).
Conclusions: The results obtained indicate that students are
somewhat hesitant with respect to online lectures as the main mode
of instruction. Lectures, generally, place students in a passive role,
which is further increased in online delivery. In order to support
students’ engagement and success, online lectures should be
combined with more active instructional strategies.
PB  - European Association of Faculties of Pharmacy
C3  - EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
T1  - Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4375
ER  - 
@conference{
author = "Malenović, Anđelija and Kovačević, Milena and Ivanović, Nevena and Protić, Ana and Parojčić, Jelena",
year = "2022",
abstract = "Synchronous lectures tend to be used as the prevalent
method of online instruction, irrespective of notable differences
and obvious limitations when compared to their in-person delivery.
Study aim was to assess students’ perspective on online lectures
held during the emergency remote teaching (ERT) due to COVID-19
pandemic.
Method: Students were invited to take part in online survey related
to their experience with ERT. Survey included 25 items related to:
satisfaction (14 items), motivation (3 items), interaction with peers
and lecturers (4 items), and perceived challenges (4 items). A 5-point
Likert scale was employed. Statistical analysis was performed using
the SPSS software.
Results: A total of 387 students participated in the survey. Majority
of respondents (79.3%) were junior students. Among them, 72.6%
reported no previous experience with online learning. Although
relatively high level of satisfaction was reported (mean score
3.91±0.75), challenges were also scored relatively high (3.05±0.99),
while interaction was scored somewhat lower (2.98±0.73), and the
least mean score was observed for motivation (2.73±0.58). Students
reported having trouble to keep motivation, concentration and
focus during online lectures, which usually took long hours per day.
Interaction with peers was reported as unsatisfactory (2.48±1.46),
whereas it was more feasible with lecturers (3.24±1.42). Students
were quite satisfied with the possibility to organize their time flexibly
(71.4%), and with respect to the workload (54.5%), while they were
less convinced that online sessions provide enough opportunities
to reflect on what has been learnt (50,1% agree, 25,1% neither
agree nor disagree).
Conclusions: The results obtained indicate that students are
somewhat hesitant with respect to online lectures as the main mode
of instruction. Lectures, generally, place students in a passive role,
which is further increased in online delivery. In order to support
students’ engagement and success, online lectures should be
combined with more active instructional strategies.",
publisher = "European Association of Faculties of Pharmacy",
journal = "EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book",
title = "Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4375"
}
Malenović, A., Kovačević, M., Ivanović, N., Protić, A.,& Parojčić, J.. (2022). Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
European Association of Faculties of Pharmacy..
https://hdl.handle.net/21.15107/rcub_farfar_4375
Malenović A, Kovačević M, Ivanović N, Protić A, Parojčić J. Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4375 .
Malenović, Anđelija, Kovačević, Milena, Ivanović, Nevena, Protić, Ana, Parojčić, Jelena, "Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade." in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4375 .

Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer

Protić, Ana; Milenković, Milan; Rašević, Marija; Otašević, Biljana; Zečević, Mira; Krmar, Jovana; Malenović, Anđelija

(Savez farmaceutskih udruženja Srbije (SFUS), 2022)

TY  - CONF
AU  - Protić, Ana
AU  - Milenković, Milan
AU  - Rašević, Marija
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Krmar, Jovana
AU  - Malenović, Anđelija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4446
AB  - Nowadays, one of the ultimate requirements in drug analysis is rapid method
development, prompt chromatographic run time and long lasting method’s lifecycle. Special
attention should be paid to development of gradient elution (U)HPLC methods that are
commonly related to troubleshooting during the inter-laboratory method transfer. The dwell
volume difference between (U)HPLC systems is the main reason for this issue (1). The aim of
this study was to propose new gradient method development methodology with integrated
dwell volumes values in the optimization process. This is especially useful approach for
industry where is frequently known which (U)HPLC instruments will be applied for drug
analysis. Proposed methodology was tested on the model mixture which encompassed
dabigatran etexilate mesylate and its nine impurities. Experimental design methodology and
three different (U)HPLC instruments with significant dwell volume differences were utilized.
Statistically significant variables were selected with Plackett-Burman design, and along with
dwell volume values were included in D-optimal design. The separation criteria s between
adjacent peaks was selected as output for method optimization. Indirect modelling together
with Monte Carlo simulations enabled selection of optimal and robust chromatographic
conditions joint for all instruments. The optimal conditions included 24% (v/v) of initial
amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient
elution run time and pH value equal to 4.9. The proposed method utility was proved since it
was successfully validated and met all validation criteria (2).
AB  - U današnje vreme, jedan od važnih zahteva prilikom razvoja hromatografskih metoda
jeste da se razvoj uradi brzo, da vreme trajanja hromatografske analize bude kratko i da se
obezbedi dug životni ciklus metode. Posebnu pažnju treba obratiti na (U)HPLC metode sa
gradijentnim eluiranjem kod kojih se često javljaju problemi prilikom međulaboratorijskog
transfera. Glavni razlog za zahtevan transfer gradijentnih (U)HPLC metoda je razlika u
vrednostima dwell volume između (U)HPLC uređaja (1). Cilj ovog rada je bio da predloži
novu metodologiju razvoja gradijentnih (U)HPLC metoda, pri čemu će vrednosti dwell
volumes biti integrisane sa drugim ulaznim promenljivama u fazi optimizacije. Ovo bi bio
posebno koristan pristup u industriji gde se obično zna na kojim će sve (U)HPLC
instrumentima metoda biti korišćena. Metodologija je testirana na smeši dabigatran eteksilat
mezilata i njegovih devet nečistoća. Za razvoj metode korišćen je eksperimentalni dizajn i tri
različita (U)HPLC instrumenta sa značajnim razlikama u dwell volume vrednostima.
Statistički značajne ulazne promenljive su dobijene primenom Plackett‐Burman dizajna, i
zajedno sa vrednostima dwell volume su bile uključene u D‐opimal dizajn. Kriterijum
razdvajanja s između susednih parova pikova odabran je kao odgovor u odnosu na koji je
metoda optimizovana. Indirektno modelovanje zajedno sa Monte Karlo simulacijom
omoguć ilo je izbor optimalnih i robusnih hromatografskih uslova zajedničkih za sva tri
instrumenta. Oni su uključivali 24% (v/v) početnog udela acetonitrila, 54% (v/v) finalnog
udela acetonitrila, vreme trajanja gradijenta od 15 minuta i pH vrednost 4,9. Primenljivost
predložene metodologije je dokazana, jer je dobijena metoda uspešno validirana na sva tri
(U)HPLC instrumenta (2).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer
T1  - Novi pristup u razvoju (U)HPLC gradijentnih metoda koji bi omogućio uspešan transfer
VL  - 72
IS  - 4 suplement
SP  - S55
EP  - S56
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4446
ER  - 
@conference{
author = "Protić, Ana and Milenković, Milan and Rašević, Marija and Otašević, Biljana and Zečević, Mira and Krmar, Jovana and Malenović, Anđelija",
year = "2022",
abstract = "Nowadays, one of the ultimate requirements in drug analysis is rapid method
development, prompt chromatographic run time and long lasting method’s lifecycle. Special
attention should be paid to development of gradient elution (U)HPLC methods that are
commonly related to troubleshooting during the inter-laboratory method transfer. The dwell
volume difference between (U)HPLC systems is the main reason for this issue (1). The aim of
this study was to propose new gradient method development methodology with integrated
dwell volumes values in the optimization process. This is especially useful approach for
industry where is frequently known which (U)HPLC instruments will be applied for drug
analysis. Proposed methodology was tested on the model mixture which encompassed
dabigatran etexilate mesylate and its nine impurities. Experimental design methodology and
three different (U)HPLC instruments with significant dwell volume differences were utilized.
Statistically significant variables were selected with Plackett-Burman design, and along with
dwell volume values were included in D-optimal design. The separation criteria s between
adjacent peaks was selected as output for method optimization. Indirect modelling together
with Monte Carlo simulations enabled selection of optimal and robust chromatographic
conditions joint for all instruments. The optimal conditions included 24% (v/v) of initial
amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient
elution run time and pH value equal to 4.9. The proposed method utility was proved since it
was successfully validated and met all validation criteria (2)., U današnje vreme, jedan od važnih zahteva prilikom razvoja hromatografskih metoda
jeste da se razvoj uradi brzo, da vreme trajanja hromatografske analize bude kratko i da se
obezbedi dug životni ciklus metode. Posebnu pažnju treba obratiti na (U)HPLC metode sa
gradijentnim eluiranjem kod kojih se često javljaju problemi prilikom međulaboratorijskog
transfera. Glavni razlog za zahtevan transfer gradijentnih (U)HPLC metoda je razlika u
vrednostima dwell volume između (U)HPLC uređaja (1). Cilj ovog rada je bio da predloži
novu metodologiju razvoja gradijentnih (U)HPLC metoda, pri čemu će vrednosti dwell
volumes biti integrisane sa drugim ulaznim promenljivama u fazi optimizacije. Ovo bi bio
posebno koristan pristup u industriji gde se obično zna na kojim će sve (U)HPLC
instrumentima metoda biti korišćena. Metodologija je testirana na smeši dabigatran eteksilat
mezilata i njegovih devet nečistoća. Za razvoj metode korišćen je eksperimentalni dizajn i tri
različita (U)HPLC instrumenta sa značajnim razlikama u dwell volume vrednostima.
Statistički značajne ulazne promenljive su dobijene primenom Plackett‐Burman dizajna, i
zajedno sa vrednostima dwell volume su bile uključene u D‐opimal dizajn. Kriterijum
razdvajanja s između susednih parova pikova odabran je kao odgovor u odnosu na koji je
metoda optimizovana. Indirektno modelovanje zajedno sa Monte Karlo simulacijom
omoguć ilo je izbor optimalnih i robusnih hromatografskih uslova zajedničkih za sva tri
instrumenta. Oni su uključivali 24% (v/v) početnog udela acetonitrila, 54% (v/v) finalnog
udela acetonitrila, vreme trajanja gradijenta od 15 minuta i pH vrednost 4,9. Primenljivost
predložene metodologije je dokazana, jer je dobijena metoda uspešno validirana na sva tri
(U)HPLC instrumenta (2).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer, Novi pristup u razvoju (U)HPLC gradijentnih metoda koji bi omogućio uspešan transfer",
volume = "72",
number = "4 suplement",
pages = "S55-S56",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4446"
}
Protić, A., Milenković, M., Rašević, M., Otašević, B., Zečević, M., Krmar, J.,& Malenović, A.. (2022). Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S55-S56.
https://hdl.handle.net/21.15107/rcub_farfar_4446
Protić A, Milenković M, Rašević M, Otašević B, Zečević M, Krmar J, Malenović A. Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer. in Arhiv za farmaciju. 2022;72(4 suplement):S55-S56.
https://hdl.handle.net/21.15107/rcub_farfar_4446 .
Protić, Ana, Milenković, Milan, Rašević, Marija, Otašević, Biljana, Zečević, Mira, Krmar, Jovana, Malenović, Anđelija, "Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S55-S56,
https://hdl.handle.net/21.15107/rcub_farfar_4446 .

Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes

Ćirić, Ana; Medarević, Đorđe; Čalija, Bojan; Dobričić, Vladimir; Rmandić, Milena; Barudžija, Tanja; Malenović, Anđelija; Đekić, Ljiljana

(Elsevier B.V., 2021)

TY  - JOUR
AU  - Ćirić, Ana
AU  - Medarević, Đorđe
AU  - Čalija, Bojan
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Đekić, Ljiljana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3759
AB  - The effect of the entrapment procedure of a poorly water soluble drug (ibuprofen) on physicochemical and drug release performances of chitosan/xanthan polyelectrolyte complexes (PECs) was investigated to achieve controlled drug release as the ultimate goal. The formation of PECs for two drug entrapment procedures (before or after the mixing of polymers) at pH 4.6 and 5.6 and three chitosan-to-xanthan mass ratios (1:1, 1:2 and 1:3) was observed by continuous decrease in conductivity during the PECs formation and increased apparent viscosity and hysteresis values. The most extensive crosslinking was observed with ibuprofen added before the PECs formation at pH 4.6 and chitosan-to-xanthan mass ratio 1:1. The PECs prepared at polymers' mass ratios 1:2 and 1:3 had higher yield and drug entrapment efficiency. DSC and FT-IR analysis confirmed ibuprofen entrapment in PECs and the partial disruption of its crystallinity. All ibuprofen release profiles were similar, with 60–70% of drug released after 12 h, mainly by diffusion, but erosion and polymer chain relaxation were also included. Potentially optimal can be considered the PEC prepared at pH 4.6, ibuprofen entrapped before the mixing of polymers at chitosan-to-xanthan mass ratio 1:2, which provided controlled drug release by zero-order kinetics, high yield, and drug entrapment efficiency.
PB  - Elsevier B.V.
T2  - International Journal of Biological Macromolecules
T1  - Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes
VL  - 167
SP  - 547
EP  - 558
DO  - 10.1016/j.ijbiomac.2020.11.201
ER  - 
@article{
author = "Ćirić, Ana and Medarević, Đorđe and Čalija, Bojan and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Đekić, Ljiljana",
year = "2021",
abstract = "The effect of the entrapment procedure of a poorly water soluble drug (ibuprofen) on physicochemical and drug release performances of chitosan/xanthan polyelectrolyte complexes (PECs) was investigated to achieve controlled drug release as the ultimate goal. The formation of PECs for two drug entrapment procedures (before or after the mixing of polymers) at pH 4.6 and 5.6 and three chitosan-to-xanthan mass ratios (1:1, 1:2 and 1:3) was observed by continuous decrease in conductivity during the PECs formation and increased apparent viscosity and hysteresis values. The most extensive crosslinking was observed with ibuprofen added before the PECs formation at pH 4.6 and chitosan-to-xanthan mass ratio 1:1. The PECs prepared at polymers' mass ratios 1:2 and 1:3 had higher yield and drug entrapment efficiency. DSC and FT-IR analysis confirmed ibuprofen entrapment in PECs and the partial disruption of its crystallinity. All ibuprofen release profiles were similar, with 60–70% of drug released after 12 h, mainly by diffusion, but erosion and polymer chain relaxation were also included. Potentially optimal can be considered the PEC prepared at pH 4.6, ibuprofen entrapped before the mixing of polymers at chitosan-to-xanthan mass ratio 1:2, which provided controlled drug release by zero-order kinetics, high yield, and drug entrapment efficiency.",
publisher = "Elsevier B.V.",
journal = "International Journal of Biological Macromolecules",
title = "Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes",
volume = "167",
pages = "547-558",
doi = "10.1016/j.ijbiomac.2020.11.201"
}
Ćirić, A., Medarević, Đ., Čalija, B., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A.,& Đekić, L.. (2021). Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes. in International Journal of Biological Macromolecules
Elsevier B.V.., 167, 547-558.
https://doi.org/10.1016/j.ijbiomac.2020.11.201
Ćirić A, Medarević Đ, Čalija B, Dobričić V, Rmandić M, Barudžija T, Malenović A, Đekić L. Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes. in International Journal of Biological Macromolecules. 2021;167:547-558.
doi:10.1016/j.ijbiomac.2020.11.201 .
Ćirić, Ana, Medarević, Đorđe, Čalija, Bojan, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Đekić, Ljiljana, "Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes" in International Journal of Biological Macromolecules, 167 (2021):547-558,
https://doi.org/10.1016/j.ijbiomac.2020.11.201 . .
21
3
22

Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies

Janošević-Ležaić, Aleksandra; Pejić, Nataša; Goronja, Jelena; Pavun, Leposava; Ðikanović, Danijela; Malenović, Anđelija

(Macedonian Journal of Chemistry and Chemical Engineering, 2021)

TY  - JOUR
AU  - Janošević-Ležaić, Aleksandra
AU  - Pejić, Nataša
AU  - Goronja, Jelena
AU  - Pavun, Leposava
AU  - Ðikanović, Danijela
AU  - Malenović, Anđelija
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4056
AB  - The effect of acetonitrile (ACN) on the micellization of a cationic surfactant, cetyltrimethylammo-nium bromide (CTAB), in aqueous solutions at different temperatures was studied. The critical micellar concentration (CMC) as well as the degree of counter ion dissociation () of CTAB in aqueous ACN mixtures (1020 % v/v) at various temperatures (291.2298.2 K) were determined by electrical conduc-tivity measurements, while steady-state fluorescence measurements were used to determine several CMCs (for comparison) and a micellar aggregation number (Nagg) as well. At a fixed temperature, both an increase in CMC and a decrease in Nagg were observed for an increase in ACN in the solvent mixture. With a temperature increase, CMC values increased for 10 % (v/v) ACN, while for both 15 % and 20 % (v/v) ACN, CMC values were a minimum at T = 295.2 K with a temperature increase. In addition, some aspects related to the Krafft temperature behavior of CTAB in the examined micellar systems are dis-cussed.
AB  - Беше испитано влијанието на ацетонитрилот (ACN) врз мицелизацијата на катјонски сурфактант, цетилтриметиламониум бромид (CTAB), во водна средина на различни температури. Со помош на мерења на електричната спроводливост, беа определени критичната мицеларна концентрација (CMC), и степенот на дисоцијација на спротивните јони () на CTAB во водни смеси на ACN (1020 % v/v) на различни температури (291,2298,2 K), додека за определување на неколку CMC (за споредба), како и на мицеларен агрегационен број (Nagg) беа употребени рамнотежни флуоресцентни мерења. На фиксна температура беше забележано зголемување на CMC и намалување на Nagg со зголемување на ACN во смесата на растворот. Со зголемување на температурата вредностите на CMC се зголемија за 10 % (v/v) ACN, додека за 15 % и за 20 % (v/v) ACN, вредностите на CMC при зголемување на температурата на T = 295,2 K беа минимални. Покрај тоа, дискутирани се некои аспекти што се поврзани со однесувањето на температурата на Krafft на CTAB во испитуваните мицеларни системи.
PB  - Macedonian Journal of Chemistry and Chemical Engineering
T2  - Macedonian Journal of Chemistry and Chemical Engineering
T1  - Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies
T1  - Мицеларни својства на цетилтриметиламониум бромид во смесата од ацетонитрил вода: кондуктометриски и флуоресцентни студии
VL  - 40
IS  - 2
SP  - 277
EP  - 287
DO  - 10.20450/MJCCE.2021.2394
ER  - 
@article{
author = "Janošević-Ležaić, Aleksandra and Pejić, Nataša and Goronja, Jelena and Pavun, Leposava and Ðikanović, Danijela and Malenović, Anđelija",
year = "2021",
abstract = "The effect of acetonitrile (ACN) on the micellization of a cationic surfactant, cetyltrimethylammo-nium bromide (CTAB), in aqueous solutions at different temperatures was studied. The critical micellar concentration (CMC) as well as the degree of counter ion dissociation () of CTAB in aqueous ACN mixtures (1020 % v/v) at various temperatures (291.2298.2 K) were determined by electrical conduc-tivity measurements, while steady-state fluorescence measurements were used to determine several CMCs (for comparison) and a micellar aggregation number (Nagg) as well. At a fixed temperature, both an increase in CMC and a decrease in Nagg were observed for an increase in ACN in the solvent mixture. With a temperature increase, CMC values increased for 10 % (v/v) ACN, while for both 15 % and 20 % (v/v) ACN, CMC values were a minimum at T = 295.2 K with a temperature increase. In addition, some aspects related to the Krafft temperature behavior of CTAB in the examined micellar systems are dis-cussed., Беше испитано влијанието на ацетонитрилот (ACN) врз мицелизацијата на катјонски сурфактант, цетилтриметиламониум бромид (CTAB), во водна средина на различни температури. Со помош на мерења на електричната спроводливост, беа определени критичната мицеларна концентрација (CMC), и степенот на дисоцијација на спротивните јони () на CTAB во водни смеси на ACN (1020 % v/v) на различни температури (291,2298,2 K), додека за определување на неколку CMC (за споредба), како и на мицеларен агрегационен број (Nagg) беа употребени рамнотежни флуоресцентни мерења. На фиксна температура беше забележано зголемување на CMC и намалување на Nagg со зголемување на ACN во смесата на растворот. Со зголемување на температурата вредностите на CMC се зголемија за 10 % (v/v) ACN, додека за 15 % и за 20 % (v/v) ACN, вредностите на CMC при зголемување на температурата на T = 295,2 K беа минимални. Покрај тоа, дискутирани се некои аспекти што се поврзани со однесувањето на температурата на Krafft на CTAB во испитуваните мицеларни системи.",
publisher = "Macedonian Journal of Chemistry and Chemical Engineering",
journal = "Macedonian Journal of Chemistry and Chemical Engineering",
title = "Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies, Мицеларни својства на цетилтриметиламониум бромид во смесата од ацетонитрил вода: кондуктометриски и флуоресцентни студии",
volume = "40",
number = "2",
pages = "277-287",
doi = "10.20450/MJCCE.2021.2394"
}
Janošević-Ležaić, A., Pejić, N., Goronja, J., Pavun, L., Ðikanović, D.,& Malenović, A.. (2021). Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies. in Macedonian Journal of Chemistry and Chemical Engineering
Macedonian Journal of Chemistry and Chemical Engineering., 40(2), 277-287.
https://doi.org/10.20450/MJCCE.2021.2394
Janošević-Ležaić A, Pejić N, Goronja J, Pavun L, Ðikanović D, Malenović A. Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies. in Macedonian Journal of Chemistry and Chemical Engineering. 2021;40(2):277-287.
doi:10.20450/MJCCE.2021.2394 .
Janošević-Ležaić, Aleksandra, Pejić, Nataša, Goronja, Jelena, Pavun, Leposava, Ðikanović, Danijela, Malenović, Anđelija, "Micellar properties of cetyltrimethylammonium bromide in an acetonitrile-water mixture: conductometric and fluorescence studies" in Macedonian Journal of Chemistry and Chemical Engineering, 40, no. 2 (2021):277-287,
https://doi.org/10.20450/MJCCE.2021.2394 . .

Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant

Milinković Budinčić, Jelena; Petrović, Lidija; Đekić, Ljiljana; Aleksić, Milijana; Fraj, Jadranka; Popović, Senka; Bučko, Sandra; Katona, Jaroslav; Spasojević, Ljiljana; Škrbić, Jelena; Malenović, Anđelija

(MDPI, 2021)

TY  - JOUR
AU  - Milinković Budinčić, Jelena
AU  - Petrović, Lidija
AU  - Đekić, Ljiljana
AU  - Aleksić, Milijana
AU  - Fraj, Jadranka
AU  - Popović, Senka
AU  - Bučko, Sandra
AU  - Katona, Jaroslav
AU  - Spasojević, Ljiljana
AU  - Škrbić, Jelena
AU  - Malenović, Anđelija
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4021
AB  - Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use in microcapsule wall design. In this study, Ch/sodium dodecyl sulfate (SDS) microcapsules, without and with cross-linking agent (formaldehyde (FA) or glutaraldehyde (GA)), were obtained by the spray drying of vitamin E loaded oil-in-water emulsion. All of the microcapsules had good stability during the drying process. Depending on the composition, their product yield, moisture content, and encapsulation efficiency varied between 11–34%, 1.14–1.62%, and 94–126%, respectively. SEM and FTIR analysis results indicate that SDS as well as cross-linkers significantly affected the microcapsule wall properties. The profiles of in vitro vitamin E release from the investigated microcapsules fit with the Korsmeyer-Peppas model (r2 > 0.9). The chemical structure of the anionic surfactant was found to have a significant effect on the vitamin E release mechanism. Ch/SDS coacervates may build a microcapsule wall without toxic crosslinkers. This enabled the combined diffusion/swelling based release mechanism of the encapsulated lipophilic substance, which can be considered favorable for utilization in food and pharmaceutical products.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant
VL  - 15
IS  - 1
DO  - 10.3390/ph15010054
ER  - 
@article{
author = "Milinković Budinčić, Jelena and Petrović, Lidija and Đekić, Ljiljana and Aleksić, Milijana and Fraj, Jadranka and Popović, Senka and Bučko, Sandra and Katona, Jaroslav and Spasojević, Ljiljana and Škrbić, Jelena and Malenović, Anđelija",
year = "2021",
abstract = "Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use in microcapsule wall design. In this study, Ch/sodium dodecyl sulfate (SDS) microcapsules, without and with cross-linking agent (formaldehyde (FA) or glutaraldehyde (GA)), were obtained by the spray drying of vitamin E loaded oil-in-water emulsion. All of the microcapsules had good stability during the drying process. Depending on the composition, their product yield, moisture content, and encapsulation efficiency varied between 11–34%, 1.14–1.62%, and 94–126%, respectively. SEM and FTIR analysis results indicate that SDS as well as cross-linkers significantly affected the microcapsule wall properties. The profiles of in vitro vitamin E release from the investigated microcapsules fit with the Korsmeyer-Peppas model (r2 > 0.9). The chemical structure of the anionic surfactant was found to have a significant effect on the vitamin E release mechanism. Ch/SDS coacervates may build a microcapsule wall without toxic crosslinkers. This enabled the combined diffusion/swelling based release mechanism of the encapsulated lipophilic substance, which can be considered favorable for utilization in food and pharmaceutical products.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant",
volume = "15",
number = "1",
doi = "10.3390/ph15010054"
}
Milinković Budinčić, J., Petrović, L., Đekić, L., Aleksić, M., Fraj, J., Popović, S., Bučko, S., Katona, J., Spasojević, L., Škrbić, J.,& Malenović, A.. (2021). Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant. in Pharmaceuticals
MDPI., 15(1).
https://doi.org/10.3390/ph15010054
Milinković Budinčić J, Petrović L, Đekić L, Aleksić M, Fraj J, Popović S, Bučko S, Katona J, Spasojević L, Škrbić J, Malenović A. Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant. in Pharmaceuticals. 2021;15(1).
doi:10.3390/ph15010054 .
Milinković Budinčić, Jelena, Petrović, Lidija, Đekić, Ljiljana, Aleksić, Milijana, Fraj, Jadranka, Popović, Senka, Bučko, Sandra, Katona, Jaroslav, Spasojević, Ljiljana, Škrbić, Jelena, Malenović, Anđelija, "Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile— Understanding the Effect of Anionic Surfactant" in Pharmaceuticals, 15, no. 1 (2021),
https://doi.org/10.3390/ph15010054 . .
1
9
10

The novel approach towards gradient elution HPLC method development

Milenković, Milan; Đajić, Nevena; Krmar, Jovana; Rašević, Marija; Malenović, Anđelija; Otašević, Biljana; Protić, Ana

(Ankara University Faculty of Pharmacy, 2021)

TY  - CONF
AU  - Milenković, Milan
AU  - Đajić, Nevena
AU  - Krmar, Jovana
AU  - Rašević, Marija
AU  - Malenović, Anđelija
AU  - Otašević, Biljana
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4696
AB  - Introduction: Gradient elution HPLC finds its
purpose in simultaneous analyses of solutes
covering wide range of polarities. However, the
instrument related factors, especially dwell volume, are frequently responsible for fizzy transfer and
short life cycle of the gradient elution method.
Therefore, it is advisable to incorporate dwell
volume into the optimization stage and avoid
transfer related failures. The chemometric
approach would enable selection of optimal
chromatographic conditions for different HPLC
instruments. The aim of this study was to propose
and test this approach in gradient elution method’s
development.
Materials and Methods: The experiments were
carried out on three chromatographic systems
(UPLC, UHPLC and HPLC), while the separation
was achieved on Kinetex C18 Core-shell column
(100 mm × 2.1 mm, 2.6 μm particle size). Design
of experiments was constructed in Design-Expert
11.0. Indirect modeling, grid point search and
graphical presentations were done in Matlab
7.10.0.
Results: Dabigatrane etexilate mesylate and nine
structurally related compounds were selected as
suitable model mixture due to its complexity and
polarity. Method development was supported with
experimental design methodology, Placket –
Burman for screening and D-optimal design for
optimization purposes. Dwell volumes were
included in the optimization phase and in this way
the same optimal chromatographic conditions for
all three instruments were selected. They included 10 mM ammonium acetate buffer
with pH set to 4.9 using acetic acid, and
acetonitrile. The components of the mobile phase
were pumped into chromatographic system with
flow rate of 400 μL min-1 in a linear gradient mode:
at 0 minutes 24% (v/v) acetonitrile and 76% (v/v) of
buffer solution, at 15 minutes 54% (v/v) acetonitrile
and 46% (v/v) buffer solution. At 16 minutes the
acetonitrile content was back to 24% (v/v) and 76%
(v/v) of buffer solution. The re-equilibration time
was set to 5 minutes. The examined
chromatographic region is graphically presented
and optimal conditions are noticed as the cross
sections (yellow dots). The method was validated
and confirmed its utility on all instruments.
Conclusions: The proposed methodology
demonstrated its ability to predict joint optimal
chromatographic conditions for instruments with different values of dwell volume. The potential was
confirmed on complex model mixture and
instruments significantly differing in dwell volume
values. In this way the gap between developing
and routine needs could be overwhelmed, followed
by facilitated transfer of methods.
PB  - Ankara University Faculty of Pharmacy
C3  - 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey
T1  - The novel approach towards gradient elution HPLC method development
SP  - 227
EP  - 228
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4696
ER  - 
@conference{
author = "Milenković, Milan and Đajić, Nevena and Krmar, Jovana and Rašević, Marija and Malenović, Anđelija and Otašević, Biljana and Protić, Ana",
year = "2021",
abstract = "Introduction: Gradient elution HPLC finds its
purpose in simultaneous analyses of solutes
covering wide range of polarities. However, the
instrument related factors, especially dwell volume, are frequently responsible for fizzy transfer and
short life cycle of the gradient elution method.
Therefore, it is advisable to incorporate dwell
volume into the optimization stage and avoid
transfer related failures. The chemometric
approach would enable selection of optimal
chromatographic conditions for different HPLC
instruments. The aim of this study was to propose
and test this approach in gradient elution method’s
development.
Materials and Methods: The experiments were
carried out on three chromatographic systems
(UPLC, UHPLC and HPLC), while the separation
was achieved on Kinetex C18 Core-shell column
(100 mm × 2.1 mm, 2.6 μm particle size). Design
of experiments was constructed in Design-Expert
11.0. Indirect modeling, grid point search and
graphical presentations were done in Matlab
7.10.0.
Results: Dabigatrane etexilate mesylate and nine
structurally related compounds were selected as
suitable model mixture due to its complexity and
polarity. Method development was supported with
experimental design methodology, Placket –
Burman for screening and D-optimal design for
optimization purposes. Dwell volumes were
included in the optimization phase and in this way
the same optimal chromatographic conditions for
all three instruments were selected. They included 10 mM ammonium acetate buffer
with pH set to 4.9 using acetic acid, and
acetonitrile. The components of the mobile phase
were pumped into chromatographic system with
flow rate of 400 μL min-1 in a linear gradient mode:
at 0 minutes 24% (v/v) acetonitrile and 76% (v/v) of
buffer solution, at 15 minutes 54% (v/v) acetonitrile
and 46% (v/v) buffer solution. At 16 minutes the
acetonitrile content was back to 24% (v/v) and 76%
(v/v) of buffer solution. The re-equilibration time
was set to 5 minutes. The examined
chromatographic region is graphically presented
and optimal conditions are noticed as the cross
sections (yellow dots). The method was validated
and confirmed its utility on all instruments.
Conclusions: The proposed methodology
demonstrated its ability to predict joint optimal
chromatographic conditions for instruments with different values of dwell volume. The potential was
confirmed on complex model mixture and
instruments significantly differing in dwell volume
values. In this way the gap between developing
and routine needs could be overwhelmed, followed
by facilitated transfer of methods.",
publisher = "Ankara University Faculty of Pharmacy",
journal = "13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey",
title = "The novel approach towards gradient elution HPLC method development",
pages = "227-228",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4696"
}
Milenković, M., Đajić, N., Krmar, J., Rašević, M., Malenović, A., Otašević, B.,& Protić, A.. (2021). The novel approach towards gradient elution HPLC method development. in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey
Ankara University Faculty of Pharmacy., 227-228.
https://hdl.handle.net/21.15107/rcub_farfar_4696
Milenković M, Đajić N, Krmar J, Rašević M, Malenović A, Otašević B, Protić A. The novel approach towards gradient elution HPLC method development. in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey. 2021;:227-228.
https://hdl.handle.net/21.15107/rcub_farfar_4696 .
Milenković, Milan, Đajić, Nevena, Krmar, Jovana, Rašević, Marija, Malenović, Anđelija, Otašević, Biljana, Protić, Ana, "The novel approach towards gradient elution HPLC method development" in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey (2021):227-228,
https://hdl.handle.net/21.15107/rcub_farfar_4696 .

A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography

Đajić, Nevena; Petković, Miloš; Zečević, Mira; Otašević, Biljana; Malenović, Anđelija; Holzgrabe, Ulrike; Protić, Ana

(Elsevier B.V., 2021)

TY  - JOUR
AU  - Đajić, Nevena
AU  - Petković, Miloš
AU  - Zečević, Mira
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Holzgrabe, Ulrike
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3822
AB  - The quantitative structure-retention relationship (QSRR) models are not only employed in retention behaviour prediction, but also in an in-depth understanding of complex chromatographic systems. The goal of the present research is to enable the comprehensive understanding of retention underlying the separation in β-cyclodextrin (CD) modified reversed-phase high performance liquid chromatography (RP-HPLC) systems, through the development of mixed QSRR models. Moreover, the amount of β-CD adsorbed on the stationary phase surface (β-CDA) is added as the model's input in order to evaluate its contribution to both model performances and retention. Nuclear magnetic resonance (NMR) experiments were conducted to confirm the predicted inclusion complex structures and support the application of in silico tools. The most significant descriptors revealed that retention is governed by the steric factors 7.5 Å distant from the geometrical centre of a molecule, 3D arrangement of atoms determining the molecular size and shape, lipophilicity indicated by topological distances, as well as the unbound system's energy, related to the inclusion complex formation. In addition, a notable effect of the pH of the aqueous phase on the retention of ionizable analytes was shown. In the case of pH of the aqueous phase and β-CDA the change in retention behaviour of the studied analytes was observed only at the highest β-CDA value (5.17 μM/m2), but it was not related to the ionization state of analytes. When the analytes did not change the ionization form across the investigated studied pH range, and the acetonitrile content in the mobile phase was 25% (v/v), the retention factor had low values regardless of the β-CDA; under these circumstances the retention is probably acetonitrile driven.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography
VL  - 1645
DO  - 10.1016/j.chroma.2021.462120
ER  - 
@article{
author = "Đajić, Nevena and Petković, Miloš and Zečević, Mira and Otašević, Biljana and Malenović, Anđelija and Holzgrabe, Ulrike and Protić, Ana",
year = "2021",
abstract = "The quantitative structure-retention relationship (QSRR) models are not only employed in retention behaviour prediction, but also in an in-depth understanding of complex chromatographic systems. The goal of the present research is to enable the comprehensive understanding of retention underlying the separation in β-cyclodextrin (CD) modified reversed-phase high performance liquid chromatography (RP-HPLC) systems, through the development of mixed QSRR models. Moreover, the amount of β-CD adsorbed on the stationary phase surface (β-CDA) is added as the model's input in order to evaluate its contribution to both model performances and retention. Nuclear magnetic resonance (NMR) experiments were conducted to confirm the predicted inclusion complex structures and support the application of in silico tools. The most significant descriptors revealed that retention is governed by the steric factors 7.5 Å distant from the geometrical centre of a molecule, 3D arrangement of atoms determining the molecular size and shape, lipophilicity indicated by topological distances, as well as the unbound system's energy, related to the inclusion complex formation. In addition, a notable effect of the pH of the aqueous phase on the retention of ionizable analytes was shown. In the case of pH of the aqueous phase and β-CDA the change in retention behaviour of the studied analytes was observed only at the highest β-CDA value (5.17 μM/m2), but it was not related to the ionization state of analytes. When the analytes did not change the ionization form across the investigated studied pH range, and the acetonitrile content in the mobile phase was 25% (v/v), the retention factor had low values regardless of the β-CDA; under these circumstances the retention is probably acetonitrile driven.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography",
volume = "1645",
doi = "10.1016/j.chroma.2021.462120"
}
Đajić, N., Petković, M., Zečević, M., Otašević, B., Malenović, A., Holzgrabe, U.,& Protić, A.. (2021). A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography. in Journal of Chromatography A
Elsevier B.V.., 1645.
https://doi.org/10.1016/j.chroma.2021.462120
Đajić N, Petković M, Zečević M, Otašević B, Malenović A, Holzgrabe U, Protić A. A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography. in Journal of Chromatography A. 2021;1645.
doi:10.1016/j.chroma.2021.462120 .
Đajić, Nevena, Petković, Miloš, Zečević, Mira, Otašević, Biljana, Malenović, Anđelija, Holzgrabe, Ulrike, Protić, Ana, "A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography" in Journal of Chromatography A, 1645 (2021),
https://doi.org/10.1016/j.chroma.2021.462120 . .
3
2

QSRR-ANN modelling in β-CD-modified RP-HPLC

Đajić, Nevena; Krmar, Jovana; Otašević, Biljana; Malenović, Anđelija; Protić, Ana

(Ankara University Faculty of Pharmacy, 2021)

TY  - JOUR
AU  - Đajić, Nevena
AU  - Krmar, Jovana
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4694
AB  - Introduction: Cyclodextrin (CD) added to RPHPLC
mobile phase interacts with analytes,
solvent components and stationary phase surface.
Therefore, the retention is influenced by the
analyte’s distribution between CD dissolved in the
mobile phase, free CD and formed inclusion
complex adsorbed onto the stationary phase, and
stationary phase itself (1, 2). The research goal
was to reveal the structural characteristics affecting
the inclusion complexation and retention in these
kinds of chromatographic systems by employing
QSRR-ANN models. Materials and Methods: Mixed QSRR model
included large pool of molecular descriptors,
complex association constants and experimental
parameters towards the retention factor of
risperidone, olanzapine and structurally related
impurities. The experimental space was
adequately covered with central composite design,
while experiments were conducted on Dionex
Ultimate 3000 (U) HPLC. QSRR-ANN modelling
was performed in STATISTICA Neural Networks.
Results: To evaluate the individual influence of
each of the descriptors, the difference in the
highest and lowest retention factor value across
the investigated range of the descriptor’s values
was calculated. The highest ratios were associated
with the following descriptors RDF075m, UE,
Mor04v and CATS2D_08_PL, making them the
most contributing towards the selected output.
RDF075m descriptor shows the three-dimensional
mass distribution calculated at a distance of 7.5 Å
from the geometrical centre of the molecule and it
refers to steric factors at the same distance.
Groups approximately 7.5 Å distant from the
geometrical centre of risperidone, olanzapine and
related compounds in their optimized
conformations were determined. These groups
were the same ones involved in the complexation
process according to previously performed NMR
study. Identified groups and their steric factors are
the most important for the formation of inclusion
complexes, and, in this way, the value of RDF075m
contributes to the retention of the selected
compounds. The importance of Mor04v confirms
the influence of molecular size and shape in
retention in these kinds of chromatographic
systems, while CATS2D_08_PL accounts for
lipophilicity.
Conclusions: The current study resulted in
development of QSRR-ANN with remarkable
performances, which enabled the elucidation of the
molecular features significantly influencing the
retention in β-CD-modified RP-HPLC. The
pronounced effect of molecular structure on
retention was best described through RDF075m,
followed by UE, Mor04v and CATS2D_08_PL.
Retention behaviour is also highly affected by
molecular size and shape, as well as lipophilicity of
the investigated compounds. Moreover, the size
and polarity of the chosen CD should not be
neglected, due to the consequent structural fit.
PB  - Ankara University Faculty of Pharmacy
T2  - The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event
T1  - QSRR-ANN modelling in β-CD-modified RP-HPLC
SP  - 104
EP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4694
ER  - 
@article{
author = "Đajić, Nevena and Krmar, Jovana and Otašević, Biljana and Malenović, Anđelija and Protić, Ana",
year = "2021",
abstract = "Introduction: Cyclodextrin (CD) added to RPHPLC
mobile phase interacts with analytes,
solvent components and stationary phase surface.
Therefore, the retention is influenced by the
analyte’s distribution between CD dissolved in the
mobile phase, free CD and formed inclusion
complex adsorbed onto the stationary phase, and
stationary phase itself (1, 2). The research goal
was to reveal the structural characteristics affecting
the inclusion complexation and retention in these
kinds of chromatographic systems by employing
QSRR-ANN models. Materials and Methods: Mixed QSRR model
included large pool of molecular descriptors,
complex association constants and experimental
parameters towards the retention factor of
risperidone, olanzapine and structurally related
impurities. The experimental space was
adequately covered with central composite design,
while experiments were conducted on Dionex
Ultimate 3000 (U) HPLC. QSRR-ANN modelling
was performed in STATISTICA Neural Networks.
Results: To evaluate the individual influence of
each of the descriptors, the difference in the
highest and lowest retention factor value across
the investigated range of the descriptor’s values
was calculated. The highest ratios were associated
with the following descriptors RDF075m, UE,
Mor04v and CATS2D_08_PL, making them the
most contributing towards the selected output.
RDF075m descriptor shows the three-dimensional
mass distribution calculated at a distance of 7.5 Å
from the geometrical centre of the molecule and it
refers to steric factors at the same distance.
Groups approximately 7.5 Å distant from the
geometrical centre of risperidone, olanzapine and
related compounds in their optimized
conformations were determined. These groups
were the same ones involved in the complexation
process according to previously performed NMR
study. Identified groups and their steric factors are
the most important for the formation of inclusion
complexes, and, in this way, the value of RDF075m
contributes to the retention of the selected
compounds. The importance of Mor04v confirms
the influence of molecular size and shape in
retention in these kinds of chromatographic
systems, while CATS2D_08_PL accounts for
lipophilicity.
Conclusions: The current study resulted in
development of QSRR-ANN with remarkable
performances, which enabled the elucidation of the
molecular features significantly influencing the
retention in β-CD-modified RP-HPLC. The
pronounced effect of molecular structure on
retention was best described through RDF075m,
followed by UE, Mor04v and CATS2D_08_PL.
Retention behaviour is also highly affected by
molecular size and shape, as well as lipophilicity of
the investigated compounds. Moreover, the size
and polarity of the chosen CD should not be
neglected, due to the consequent structural fit.",
publisher = "Ankara University Faculty of Pharmacy",
journal = "The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event",
title = "QSRR-ANN modelling in β-CD-modified RP-HPLC",
pages = "104-105",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4694"
}
Đajić, N., Krmar, J., Otašević, B., Malenović, A.,& Protić, A.. (2021). QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event
Ankara University Faculty of Pharmacy., 104-105.
https://hdl.handle.net/21.15107/rcub_farfar_4694
Đajić N, Krmar J, Otašević B, Malenović A, Protić A. QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event. 2021;:104-105.
https://hdl.handle.net/21.15107/rcub_farfar_4694 .
Đajić, Nevena, Krmar, Jovana, Otašević, Biljana, Malenović, Anđelija, Protić, Ana, "QSRR-ANN modelling in β-CD-modified RP-HPLC" in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event (2021):104-105,
https://hdl.handle.net/21.15107/rcub_farfar_4694 .

Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC

Đajić, Nevena; Otašević, Biljana; Malenović, Anđelija; Zečević, Mira; Holzgrabe, Ulrike; Protić, Ana

(Elsevier B.V., 2021)

TY  - JOUR
AU  - Đajić, Nevena
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Zečević, Mira
AU  - Holzgrabe, Ulrike
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3728
AB  - Binding between cyclodextrin (CD) cavity and guest molecule in Reversed Phase High-Performance Liquid Chromatography (RP-HPLC) is dynamic process. In general, increasing CD concentration is inducing inclusion complex formation, leading to reduction of analyte's retention time. Consequently, the shortness in retention time is a measure of complex stability in HPLC. However, under certain experimental conditions, the retention of some analytes could be prolonged even when concentration of CD in the mobile phase is increased. In order to reveal the cause of this unexpected retention behavior, the present study was carried on. The model mixture consisted of risperidone, olanzapine and their related impurities, while β-CD was selected among CDs, as in the previous study. In order to achieve fast equilibrium between free analyte and β-CD-analyte complex, β-CD was not added to the mobile phase, but only to the sample. Detection was performed with Corona Charged Aerosol Detector (CAD), suitable for non-chromophoric β-CD. When analyzing olanzapine impurity B-β-CD sample, three peaks were detected, namely free β-CD, β-CD-analyte complex and free analyte. The complex stability constant was calculated employing a modification of the Benesi-Hildebrandt equation and CAD has proven to be useful in complex stability constants assessment if retention of free analyte and β-CD-analyte complex is distinguished. For all other analytes only two peaks could be detected, because free analyte and formed complex are eluting at the same retention time. Under such circumstances, the authors proposed the methodology for calculating stability constants and confirmed its applicability to studied model mixture.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC
VL  - 193
DO  - 10.1016/j.jpba.2020.113711
ER  - 
@article{
author = "Đajić, Nevena and Otašević, Biljana and Malenović, Anđelija and Zečević, Mira and Holzgrabe, Ulrike and Protić, Ana",
year = "2021",
abstract = "Binding between cyclodextrin (CD) cavity and guest molecule in Reversed Phase High-Performance Liquid Chromatography (RP-HPLC) is dynamic process. In general, increasing CD concentration is inducing inclusion complex formation, leading to reduction of analyte's retention time. Consequently, the shortness in retention time is a measure of complex stability in HPLC. However, under certain experimental conditions, the retention of some analytes could be prolonged even when concentration of CD in the mobile phase is increased. In order to reveal the cause of this unexpected retention behavior, the present study was carried on. The model mixture consisted of risperidone, olanzapine and their related impurities, while β-CD was selected among CDs, as in the previous study. In order to achieve fast equilibrium between free analyte and β-CD-analyte complex, β-CD was not added to the mobile phase, but only to the sample. Detection was performed with Corona Charged Aerosol Detector (CAD), suitable for non-chromophoric β-CD. When analyzing olanzapine impurity B-β-CD sample, three peaks were detected, namely free β-CD, β-CD-analyte complex and free analyte. The complex stability constant was calculated employing a modification of the Benesi-Hildebrandt equation and CAD has proven to be useful in complex stability constants assessment if retention of free analyte and β-CD-analyte complex is distinguished. For all other analytes only two peaks could be detected, because free analyte and formed complex are eluting at the same retention time. Under such circumstances, the authors proposed the methodology for calculating stability constants and confirmed its applicability to studied model mixture.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC",
volume = "193",
doi = "10.1016/j.jpba.2020.113711"
}
Đajić, N., Otašević, B., Malenović, A., Zečević, M., Holzgrabe, U.,& Protić, A.. (2021). Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 193.
https://doi.org/10.1016/j.jpba.2020.113711
Đajić N, Otašević B, Malenović A, Zečević M, Holzgrabe U, Protić A. Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC. in Journal of Pharmaceutical and Biomedical Analysis. 2021;193.
doi:10.1016/j.jpba.2020.113711 .
Đajić, Nevena, Otašević, Biljana, Malenović, Anđelija, Zečević, Mira, Holzgrabe, Ulrike, Protić, Ana, "Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC" in Journal of Pharmaceutical and Biomedical Analysis, 193 (2021),
https://doi.org/10.1016/j.jpba.2020.113711 . .
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