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 . .

TY  - CONF
AU  - Stojanović, Jevrem
AU  - Zalewski, Przemysław
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Malenović, Anđelija
AU  - Janošević-Ležaić, Aleksandra
AU  - Ranđelović, Dragana
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 - „Modern pharmaceutical and biomedical analytics in health care”
T1  - Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline
SP  - 64
EP  - 64
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5479
ER  - 

@conference{
author = "Stojanović, Jevrem and Zalewski, Przemysław and Otašević, Biljana and Zečević, Mira and Malenović, Anđelija and Janošević-Ležaić, Aleksandra and Ranđelović, Dragana 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 - „Modern pharmaceutical and biomedical analytics in health care”",
title = "Adsorption of pharmaceuticals by novel carbonaceous materials from the leaves of  Ailanthus altissima (Mill.) Swingle - Case study on the adsorption of tetracycline",
pages = "64-64",
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 - „Modern pharmaceutical and biomedical analytics in health care”
Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu., 64-64.
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 - „Modern pharmaceutical and biomedical analytics in health care”. 2023;:64-64.
https://hdl.handle.net/21.15107/rcub_farfar_5479 .

Stojanović, Jevrem, Zalewski, Przemysław, Otašević, Biljana, Zečević, Mira, Malenović, Anđelija, Janošević-Ležaić, Aleksandra, Ranđelović, Dragana, 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 - „Modern pharmaceutical and biomedical analytics in health care” (2023):64-64,
https://hdl.handle.net/21.15107/rcub_farfar_5479 .

TY  - JOUR
AU  - Mijatović, Vesna
AU  - Zečević, Mira
AU  - Zirojević, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4977
AB  - The goal of this study was the optimization of chromatographic conditions and validation
of the isocratic RP-HPLC method for monitoring the stability of aripiprazole, identification and
quantitative analysis of aripiprazole and its degradation products in tablets.
In addition, robustness was tested by applying the methodology of experimental design.
The forced degradation study of aripiprazole was conducted in accordance with the ICH
guidelines. The stability of the active pharmaceutical substance was tested under the conditions
of hydrolysis in acidic, neutral and basic environments, thermal degradation, oxidation and
photolysis. The active pharmaceutical ingredient was degraded under oxidation conditions, and
the identity of the resulting degradation product, N-oxide, was confirmed. Under the other
conditions tested, the active pharmaceutical substance was found to be stable. The developed
method RP-HPLC allowed the separation of degradation products and aripiprazole and was
defined as a stability-indicating method. The proposed method was validated for qualitative and
quantitative analysis of aripiprazole and its degradation products. Accordingly, selectivity,
linearity, precision, accuracy, limit of detection, limit of quantification, and robustness of the
method were tested. The Box-Behnken experimental design was used in robustness testing.
AB  - Cilj rada bio je optimizacija hromatografskih uslova i validacija izokratske HPLC metode
za praćenje stabilnosti aripiprazola, identifikacija i kvantitativna analiza aripiprazola i njegovih
degradacionih proizvoda u tabletama, kao i ispitivanje robusnosti predložene analitičke metode
primenom eksperimentalnog dizajna.
Studija forsirane degradacije aktivne farmaceutske supstance aripiprazola sprovedena je u
skladu sa ICH smernicama. Ispitivana je stabilnost aktivne supstance u uslovima hidrolize u
kiseloj, neutralnoj i baznoj sredini, termalne degradacije, oksidacije i fotolize. Aktivna supstanca
je pokazala degradaciju u uslovima oksidacije, pri čemu je potvrđen identitet nastalog proizvoda,
N-oksida, Pri ostalim ispitivanim uslovima, aktivna farmaceutska supstanca je pokazala
stabilnost. Kako je predložena RP-HPLC metoda omogućila efikasno razdvajanje degradacionih
proizvoda i aripiprazola, definisana je kao metoda za praćenje stabilnosti farmaceutskog
proizvoda.
Sprovedena je validacija predložene metode za istovremenu identifikaciju i kvantifikaciju
aripiprazola i njegovih degradacionih proizvoda. Tom prilikom su ispitani selektivnost,
linearnost, preciznost, tačnost, limit detekcije i limit kvantifikacije, a primenom Box-
Behnkenovog eksperimentalnog dizajna ispitana je i robusnost metode.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products
T1  - Razvoj i validacija RP-HPLC metode za praćenje stabilnosti u cilju određivanja sadržaja aripiprazola i njegovih degradacionih proizvoda
VL  - 73
IS  - 3
SP  - 216
EP  - 235
DO  - 10.5937/arhfarm73-44512
ER  - 

@article{
author = "Mijatović, Vesna and Zečević, Mira and Zirojević, Jelena",
year = "2023",
abstract = "The goal of this study was the optimization of chromatographic conditions and validation
of the isocratic RP-HPLC method for monitoring the stability of aripiprazole, identification and
quantitative analysis of aripiprazole and its degradation products in tablets.
In addition, robustness was tested by applying the methodology of experimental design.
The forced degradation study of aripiprazole was conducted in accordance with the ICH
guidelines. The stability of the active pharmaceutical substance was tested under the conditions
of hydrolysis in acidic, neutral and basic environments, thermal degradation, oxidation and
photolysis. The active pharmaceutical ingredient was degraded under oxidation conditions, and
the identity of the resulting degradation product, N-oxide, was confirmed. Under the other
conditions tested, the active pharmaceutical substance was found to be stable. The developed
method RP-HPLC allowed the separation of degradation products and aripiprazole and was
defined as a stability-indicating method. The proposed method was validated for qualitative and
quantitative analysis of aripiprazole and its degradation products. Accordingly, selectivity,
linearity, precision, accuracy, limit of detection, limit of quantification, and robustness of the
method were tested. The Box-Behnken experimental design was used in robustness testing., Cilj rada bio je optimizacija hromatografskih uslova i validacija izokratske HPLC metode
za praćenje stabilnosti aripiprazola, identifikacija i kvantitativna analiza aripiprazola i njegovih
degradacionih proizvoda u tabletama, kao i ispitivanje robusnosti predložene analitičke metode
primenom eksperimentalnog dizajna.
Studija forsirane degradacije aktivne farmaceutske supstance aripiprazola sprovedena je u
skladu sa ICH smernicama. Ispitivana je stabilnost aktivne supstance u uslovima hidrolize u
kiseloj, neutralnoj i baznoj sredini, termalne degradacije, oksidacije i fotolize. Aktivna supstanca
je pokazala degradaciju u uslovima oksidacije, pri čemu je potvrđen identitet nastalog proizvoda,
N-oksida, Pri ostalim ispitivanim uslovima, aktivna farmaceutska supstanca je pokazala
stabilnost. Kako je predložena RP-HPLC metoda omogućila efikasno razdvajanje degradacionih
proizvoda i aripiprazola, definisana je kao metoda za praćenje stabilnosti farmaceutskog
proizvoda.
Sprovedena je validacija predložene metode za istovremenu identifikaciju i kvantifikaciju
aripiprazola i njegovih degradacionih proizvoda. Tom prilikom su ispitani selektivnost,
linearnost, preciznost, tačnost, limit detekcije i limit kvantifikacije, a primenom Box-
Behnkenovog eksperimentalnog dizajna ispitana je i robusnost metode.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products, Razvoj i validacija RP-HPLC metode za praćenje stabilnosti u cilju određivanja sadržaja aripiprazola i njegovih degradacionih proizvoda",
volume = "73",
number = "3",
pages = "216-235",
doi = "10.5937/arhfarm73-44512"
}

Mijatović, V., Zečević, M.,& Zirojević, J.. (2023). Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(3), 216-235.
https://doi.org/10.5937/arhfarm73-44512

Mijatović V, Zečević M, Zirojević J. Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products. in Arhiv za farmaciju. 2023;73(3):216-235.
doi:10.5937/arhfarm73-44512 .

Mijatović, Vesna, Zečević, Mira, Zirojević, Jelena, "Development and validation of a stability- indicating RP-HPLC method for determination of aripiprazole and its degradation products" in Arhiv za farmaciju, 73, no. 3 (2023):216-235,
https://doi.org/10.5937/arhfarm73-44512 . .

TY  - JOUR
AU  - Salkić, Alma
AU  - Otašević, Biljana
AU  - Rašević, Marija
AU  - Zečević, Mira
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5143
AB  - A selective eco-friendly micellar HPLC method was developed for investigation of moxifloxacin and related compounds in the presence of its degradation products. Central composite design was used to optimize the experimental conditions. The proposed method is based on isocratic elution on a C18 column using 92.5% (v/v) biodegradable aqueous mobile phase containing 0.01 M sodium dihydrogen phosphate, 0.15 M sodium dodecyl sulfate (SDS) and 0.5% triethylamine (v/v) with a pH of 3.5 and 7.5% isopropanol (v/v) as eco- friendly organic solvent. The flow rate and injection volume were 0.6 ml/min and 5 µl, respectively. Experiments were performed at a temperature of 60 °C and detection was performed at 295 nm. The optimized method was validated. The method was found to be suitable for the quantification of moxifloxacin and its related compounds in moxifloxacin drug substance. The Green Analytical Procedure Index (GAPI) proves the superiority of the developed method against other reported methods.
PB  - Slovensko Kemijsko Drustvo
T2  - Acta Chimica Slovenica
T1  - Micellar Liquid Chromatographic Method for Determination of Moxifloxacin and its Impurities
VL  - 70
IS  - 3
SP  - 385
EP  - 397
DO  - 10.17344/acsi.2023.8022
ER  - 

@article{
author = "Salkić, Alma and Otašević, Biljana and Rašević, Marija and Zečević, Mira",
year = "2023",
abstract = "A selective eco-friendly micellar HPLC method was developed for investigation of moxifloxacin and related compounds in the presence of its degradation products. Central composite design was used to optimize the experimental conditions. The proposed method is based on isocratic elution on a C18 column using 92.5% (v/v) biodegradable aqueous mobile phase containing 0.01 M sodium dihydrogen phosphate, 0.15 M sodium dodecyl sulfate (SDS) and 0.5% triethylamine (v/v) with a pH of 3.5 and 7.5% isopropanol (v/v) as eco- friendly organic solvent. The flow rate and injection volume were 0.6 ml/min and 5 µl, respectively. Experiments were performed at a temperature of 60 °C and detection was performed at 295 nm. The optimized method was validated. The method was found to be suitable for the quantification of moxifloxacin and its related compounds in moxifloxacin drug substance. The Green Analytical Procedure Index (GAPI) proves the superiority of the developed method against other reported methods.",
publisher = "Slovensko Kemijsko Drustvo",
journal = "Acta Chimica Slovenica",
title = "Micellar Liquid Chromatographic Method for Determination of Moxifloxacin and its Impurities",
volume = "70",
number = "3",
pages = "385-397",
doi = "10.17344/acsi.2023.8022"
}

Salkić, A., Otašević, B., Rašević, M.,& Zečević, M.. (2023). Micellar Liquid Chromatographic Method for Determination of Moxifloxacin and its Impurities. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo., 70(3), 385-397.
https://doi.org/10.17344/acsi.2023.8022

Salkić A, Otašević B, Rašević M, Zečević M. Micellar Liquid Chromatographic Method for Determination of Moxifloxacin and its Impurities. in Acta Chimica Slovenica. 2023;70(3):385-397.
doi:10.17344/acsi.2023.8022 .

Salkić, Alma, Otašević, Biljana, Rašević, Marija, Zečević, Mira, "Micellar Liquid Chromatographic Method for Determination of Moxifloxacin and its Impurities" in Acta Chimica Slovenica, 70, no. 3 (2023):385-397,
https://doi.org/10.17344/acsi.2023.8022 . .

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 . .

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 . .

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 . .

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 .

TY  - CONF
AU  - Otašević, Biljana
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Zečević, Mira
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4688
AB  - Liquid chromatography which implies that an analyte interacts through several
separation mechanisms (modes) with a stationary phase packed in a single chromatographic
column is called multimodal or mixed-mode chromatography (MMC). Based on the combined
modes, MMC is seen as bimodal (RP/HILIC, RP/IEX, HILIC/IEX) or trimodal (different
RP/HILIC/IEXcombinations) system. Consequently, compounds that encompass wide
spectra of properties (nonpolar, polar, organic, inorganic, ionized and/or non-ionized) can
be chromatographed in a single chromatographic run. The main practical achievement of this
is the reduction of the number of required analyses needed per one complex sample
compared to unimodal chromatographic systems. Therefore, the popularity of MMC grows
rapidly in recent years together with the number of its applications (1). Beside common
quality control issues that include active pharmaceutical ingredients and related substances
analysis and impurity profiling, the range of different analytes which MMC successfully
handles extends to the analyses of drugs in environmental and biological samples, peptides
and proteins. Since nearly half of recently FDA approved pharmaceutical substances are in
the form of a salt, the focus of MMC turned to pharmaceutical counterions analyses as well
(2). However, separations are governed by numerous intermolecular interactions resulting
from specific analyteʼs properties (size, charge, polarity) and mobile phase composition
(aqueous phase ionic strength and pH value, organic solvent content) while the quality of
separation can also be affected by column temperature and mobile phase flow rate.
Eventually, analytical method development is challenging and demands the assistance of
multifactorial optimization strategies such as the design of experiments.
AB  - Tečna hromatografija koja podrazumeva da analit interaguje putem nekoliko
mehanizama razdvajanja (modova) sa stacionarnom fazom upakovanom u jednu istu
hromatografsku kolonu naziva se multimodalna hromatografija (MMC). Na osnovu
kombinovanih modova, MMC se posmatra kao bimodalni (RP/HILIC, RP/IEX, HILIC/IEX) ili
trimodalni (različite RP/HILIC/IEX kombinacije) sistem. Ovo za posledicu ima da jedinjenja
širokog spektra svojstava (nepolarna, polarna, organska, neorganska, jonizovana i/ili
nejonizovana) mogu se hromatografisati u jednom ciklusu hromatografije. Glavni praktični
doprinos ovoga je smanjenje broja potrebnih analiza po jednom složenom uzorku u
poređenju sa unimodalnim hromatografskim sistemima. Zbog toga, popularnost MMC naglo
raste poslednjih godina zajedno sa brojem njenih aplikacija (1). Pored uobičajenih pitanja
kontrole kvaliteta koja uključuju analizu aktivnih farmaceutskih sastojaka i srodnih
supstanci i profilisanje nečistoća, opseg različitih analita sa kojima MMC uspešno pokriva
proširen je analitikom lekova iz prirodnog okruženja i bioloških uzoraka, peptidima i
proteinima. Pošto je skoro polovina farmaceutskih supstanci koje je nedavno FDA odobrila u
obliku soli, fokus MMC je orjentisan i ka analizi farmaceutskih kontrajona (2). Međutim,
hromatografsko razdvajanje je vođeno brojnim intermolekularnim interakcijima koje su
rezultat specifičnih svojstava analita (veličina, naelektrisanje, polaritet) i mobilne faze
(jonska jačina i pH vrednost vodene faze, sadržaj organskog rastvarača), dok na kvalitet
razdvajanja može uticati i temperatura kolone i brzina protoka mobilne faze. Na kraju, razvoj
analitičkih metoda predstavlja izazov i zahteva podršku u strategijama multifaktorske
optimizacije kao što je dizajn eksperimenata.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - The use of multimodal chromatography in the control of pharmaceutical products: New possibilities and new challenges
T1  - Primena multimodalne hromatografije u kontroli farmaceutskih proizvoda: Nove mogućnosti i novi izazovi
VL  - 72
IS  - suppl. 4
SP  - 57
EP  - 58
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4688
ER  - 

@conference{
author = "Otašević, Biljana and Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Zečević, Mira",
year = "2022",
abstract = "Liquid chromatography which implies that an analyte interacts through several
separation mechanisms (modes) with a stationary phase packed in a single chromatographic
column is called multimodal or mixed-mode chromatography (MMC). Based on the combined
modes, MMC is seen as bimodal (RP/HILIC, RP/IEX, HILIC/IEX) or trimodal (different
RP/HILIC/IEXcombinations) system. Consequently, compounds that encompass wide
spectra of properties (nonpolar, polar, organic, inorganic, ionized and/or non-ionized) can
be chromatographed in a single chromatographic run. The main practical achievement of this
is the reduction of the number of required analyses needed per one complex sample
compared to unimodal chromatographic systems. Therefore, the popularity of MMC grows
rapidly in recent years together with the number of its applications (1). Beside common
quality control issues that include active pharmaceutical ingredients and related substances
analysis and impurity profiling, the range of different analytes which MMC successfully
handles extends to the analyses of drugs in environmental and biological samples, peptides
and proteins. Since nearly half of recently FDA approved pharmaceutical substances are in
the form of a salt, the focus of MMC turned to pharmaceutical counterions analyses as well
(2). However, separations are governed by numerous intermolecular interactions resulting
from specific analyteʼs properties (size, charge, polarity) and mobile phase composition
(aqueous phase ionic strength and pH value, organic solvent content) while the quality of
separation can also be affected by column temperature and mobile phase flow rate.
Eventually, analytical method development is challenging and demands the assistance of
multifactorial optimization strategies such as the design of experiments., Tečna hromatografija koja podrazumeva da analit interaguje putem nekoliko
mehanizama razdvajanja (modova) sa stacionarnom fazom upakovanom u jednu istu
hromatografsku kolonu naziva se multimodalna hromatografija (MMC). Na osnovu
kombinovanih modova, MMC se posmatra kao bimodalni (RP/HILIC, RP/IEX, HILIC/IEX) ili
trimodalni (različite RP/HILIC/IEX kombinacije) sistem. Ovo za posledicu ima da jedinjenja
širokog spektra svojstava (nepolarna, polarna, organska, neorganska, jonizovana i/ili
nejonizovana) mogu se hromatografisati u jednom ciklusu hromatografije. Glavni praktični
doprinos ovoga je smanjenje broja potrebnih analiza po jednom složenom uzorku u
poređenju sa unimodalnim hromatografskim sistemima. Zbog toga, popularnost MMC naglo
raste poslednjih godina zajedno sa brojem njenih aplikacija (1). Pored uobičajenih pitanja
kontrole kvaliteta koja uključuju analizu aktivnih farmaceutskih sastojaka i srodnih
supstanci i profilisanje nečistoća, opseg različitih analita sa kojima MMC uspešno pokriva
proširen je analitikom lekova iz prirodnog okruženja i bioloških uzoraka, peptidima i
proteinima. Pošto je skoro polovina farmaceutskih supstanci koje je nedavno FDA odobrila u
obliku soli, fokus MMC je orjentisan i ka analizi farmaceutskih kontrajona (2). Međutim,
hromatografsko razdvajanje je vođeno brojnim intermolekularnim interakcijima koje su
rezultat specifičnih svojstava analita (veličina, naelektrisanje, polaritet) i mobilne faze
(jonska jačina i pH vrednost vodene faze, sadržaj organskog rastvarača), dok na kvalitet
razdvajanja može uticati i temperatura kolone i brzina protoka mobilne faze. Na kraju, razvoj
analitičkih metoda predstavlja izazov i zahteva podršku u strategijama multifaktorske
optimizacije kao što je dizajn eksperimenata.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "The use of multimodal chromatography in the control of pharmaceutical products: New possibilities and new challenges, Primena multimodalne hromatografije u kontroli farmaceutskih proizvoda: Nove mogućnosti i novi izazovi",
volume = "72",
number = "suppl. 4",
pages = "57-58",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4688"
}

Otašević, B., Svrkota, B., Krmar, J., Protić, A.,& Zečević, M.. (2022). The use of multimodal chromatography in the control of pharmaceutical products: New possibilities and new challenges. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(suppl. 4), 57-58.
https://hdl.handle.net/21.15107/rcub_farfar_4688

Otašević B, Svrkota B, Krmar J, Protić A, Zečević M. The use of multimodal chromatography in the control of pharmaceutical products: New possibilities and new challenges. in Arhiv za farmaciju. 2022;72(suppl. 4):57-58.
https://hdl.handle.net/21.15107/rcub_farfar_4688 .

Otašević, Biljana, Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Zečević, Mira, "The use of multimodal chromatography in the control of pharmaceutical products: New possibilities and new challenges" in Arhiv za farmaciju, 72, no. suppl. 4 (2022):57-58,
https://hdl.handle.net/21.15107/rcub_farfar_4688 .

TY  - JOUR
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4330
AB  - A new optimization strategy based on the mixed quantitative struc- ture–retention relationship (QSRR) model is proposed for improving the RP- HPLC separation of aripiprazole and its impurities (IMP A-E). Firstly, experi- mental parameters (EPs), namely mobile phase composition and flow rate, were varied according to Box–Behnken design and thereafter, an artificial neural network (ANN) as a QSRR model was built correlating EPs and sel- ected molecular descriptors (ovality, torsion energy and non-1,4-van der Waals energy) with the log-transformed retention times of the analytes. Values of the root mean square error (RMSE) were used for an estimation of the quality of the ANNs (0.0227, 0.0191 and 0.0230 for the training, verification and test set, respectively). The separations of critical peak pairs on chromatogram (IMP A- B and IMP D-C) were optimized using ANNs for which the EPs served as inputs and the log-transformed separation criteria s as the outputs. They were validated by application of leave-one-out cross-validation (RMSE values 0.065 and 0.056, respectively). The obtained ANNs were used for plotting response surfaces upon which the analyses chromatographic conditions resulting in optimal analytes retention behaviour and the optimal values of the separation criteria s were defined. The optimal conditions were 54 % of methanol at the beginning and 79 % of methanol at the end of gradient elution programme with a mobile phase flow rate of 460 μL min-1
AB  - Нова оптимизациона стратегија заснована на грађењу мешовитих модела за кван- тификовање односа структуре и ретенционог понашања (QSRR) предложена је за уна- пређење RP-HPLC раздвајања арипипразола и његових нечистоћа (IMP А-Е). Експери- ментални параметри (EP), састав мобилне фазе и брзина протока, варирани су најпре у складу са Box–Behnken дизајном, а затим је награђена вештачка неуронска мрежа као QSRR модел који повезује ЕP и одабране молекуларне дескрипторе (овалност, торзиона енергија и не-1,4-ван дер Валсова енергија) са логаритамски трансформисаним ретен- ционим временом аналита. Вредности средње квадратне грешке (RMSE) коришћене су за процену квалитета мреже (0,0227, 0,0191 и 0,0230 за тренинг, верификацију и тест сет, редом). Раздвајање критичних парова пикова на хроматограму (IMP А-B и IMP D-C) оптимизовано је коришћењем мрежа за које су ЕP послужили као улази, а логаритамски трансформисани критеријуми сепарације s као излази. Ове мреже су валидиране при- меном унакрсне валидације изостанка (RMSE вредности, редом, 0,065 и 0,056). На основу награђених мрежа, конструисани су дијаграми површина одговора чијом ана- лизом су дефинисани услови при којима се постиже оптимална ретенција аналита, односно вредности критеријума сепарације s, а који су подразумевали 54 % метанола на почетку и 79 % на крају програма градијентног елуирања са брзином протока мобилне фазе од 460 mL min -1
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach
T1  - Оптимизација хроматографског раздвајања арипипразола и нечистоћа: приступ квантификовања односа структуре и ретенционог понашања
VL  - 87
IS  - 5
SP  - 615
EP  - 628
DO  - 10.2298/JSC210709092S
ER  - 

@article{
author = "Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Zečević, Mira and Otašević, Biljana",
year = "2022",
abstract = "A new optimization strategy based on the mixed quantitative struc- ture–retention relationship (QSRR) model is proposed for improving the RP- HPLC separation of aripiprazole and its impurities (IMP A-E). Firstly, experi- mental parameters (EPs), namely mobile phase composition and flow rate, were varied according to Box–Behnken design and thereafter, an artificial neural network (ANN) as a QSRR model was built correlating EPs and sel- ected molecular descriptors (ovality, torsion energy and non-1,4-van der Waals energy) with the log-transformed retention times of the analytes. Values of the root mean square error (RMSE) were used for an estimation of the quality of the ANNs (0.0227, 0.0191 and 0.0230 for the training, verification and test set, respectively). The separations of critical peak pairs on chromatogram (IMP A- B and IMP D-C) were optimized using ANNs for which the EPs served as inputs and the log-transformed separation criteria s as the outputs. They were validated by application of leave-one-out cross-validation (RMSE values 0.065 and 0.056, respectively). The obtained ANNs were used for plotting response surfaces upon which the analyses chromatographic conditions resulting in optimal analytes retention behaviour and the optimal values of the separation criteria s were defined. The optimal conditions were 54 % of methanol at the beginning and 79 % of methanol at the end of gradient elution programme with a mobile phase flow rate of 460 μL min-1, Нова оптимизациона стратегија заснована на грађењу мешовитих модела за кван- тификовање односа структуре и ретенционог понашања (QSRR) предложена је за уна- пређење RP-HPLC раздвајања арипипразола и његових нечистоћа (IMP А-Е). Експери- ментални параметри (EP), састав мобилне фазе и брзина протока, варирани су најпре у складу са Box–Behnken дизајном, а затим је награђена вештачка неуронска мрежа као QSRR модел који повезује ЕP и одабране молекуларне дескрипторе (овалност, торзиона енергија и не-1,4-ван дер Валсова енергија) са логаритамски трансформисаним ретен- ционим временом аналита. Вредности средње квадратне грешке (RMSE) коришћене су за процену квалитета мреже (0,0227, 0,0191 и 0,0230 за тренинг, верификацију и тест сет, редом). Раздвајање критичних парова пикова на хроматограму (IMP А-B и IMP D-C) оптимизовано је коришћењем мрежа за које су ЕP послужили као улази, а логаритамски трансформисани критеријуми сепарације s као излази. Ове мреже су валидиране при- меном унакрсне валидације изостанка (RMSE вредности, редом, 0,065 и 0,056). На основу награђених мрежа, конструисани су дијаграми површина одговора чијом ана- лизом су дефинисани услови при којима се постиже оптимална ретенција аналита, односно вредности критеријума сепарације s, а који су подразумевали 54 % метанола на почетку и 79 % на крају програма градијентног елуирања са брзином протока мобилне фазе од 460 mL min -1",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach, Оптимизација хроматографског раздвајања арипипразола и нечистоћа: приступ квантификовања односа структуре и ретенционог понашања",
volume = "87",
number = "5",
pages = "615-628",
doi = "10.2298/JSC210709092S"
}

Svrkota, B., Krmar, J., Protić, A., Zečević, M.,& Otašević, B.. (2022). Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 87(5), 615-628.
https://doi.org/10.2298/JSC210709092S

Svrkota B, Krmar J, Protić A, Zečević M, Otašević B. Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach. in Journal of the Serbian Chemical Society. 2022;87(5):615-628.
doi:10.2298/JSC210709092S .

Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Zečević, Mira, Otašević, Biljana, "Optimization of chromatographic separation of aripiprazole and impurities: Quantitative structure-retention relationship approach" in Journal of the Serbian Chemical Society, 87, no. 5 (2022):615-628,
https://doi.org/10.2298/JSC210709092S . .

TY  - CONF
AU  - Salkić, Alma
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4695
PB  - National Institute of Chemistry, Slovenia
C3  - 26th International Symposium on Separation Sciences, 28th June - 1st July 2022, Ljubljana, Slovenia
T1  - Micellar liquid chromatographic method for determination of moxifloxacin impurities
SP  - 113
EP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4695
ER  - 

@conference{
author = "Salkić, Alma and Zečević, Mira and Otašević, Biljana",
year = "2022",
publisher = "National Institute of Chemistry, Slovenia",
journal = "26th International Symposium on Separation Sciences, 28th June - 1st July 2022, Ljubljana, Slovenia",
title = "Micellar liquid chromatographic method for determination of moxifloxacin impurities",
pages = "113-113",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4695"
}

Salkić, A., Zečević, M.,& Otašević, B.. (2022). Micellar liquid chromatographic method for determination of moxifloxacin impurities. in 26th International Symposium on Separation Sciences, 28th June - 1st July 2022, Ljubljana, Slovenia
National Institute of Chemistry, Slovenia., 113-113.
https://hdl.handle.net/21.15107/rcub_farfar_4695

Salkić A, Zečević M, Otašević B. Micellar liquid chromatographic method for determination of moxifloxacin impurities. in 26th International Symposium on Separation Sciences, 28th June - 1st July 2022, Ljubljana, Slovenia. 2022;:113-113.
https://hdl.handle.net/21.15107/rcub_farfar_4695 .

Salkić, Alma, Zečević, Mira, Otašević, Biljana, "Micellar liquid chromatographic method for determination of moxifloxacin impurities" in 26th International Symposium on Separation Sciences, 28th June - 1st July 2022, Ljubljana, Slovenia (2022):113-113,
https://hdl.handle.net/21.15107/rcub_farfar_4695 .

TY  - CONF
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4697
AB  - One of widely used drug group refers to drugs that act through adrenergic system. In following
research, the intent was to develop High Performance Liquid Chromatography (HPLC) method for
separation of adrenergic drugs. Therefore, selected mixture of analytes contained bisoprolol (BP),
fenoterole (FT), doxazosin (DOX), tetrahydrazoline (TH) and lofexidine (LOF). One of the
advantages of this method reflects in expanding knowledge about the analytical behaviour of
lofexidine, which is limited. Since all of selected analytes are basic in nature, mixed-mode column,
which includes reverse phase (RP) and weak cation exchange (WCX) interactions, was considered as
adequate for this HPLC analysis. The pronunciation one of two separation mechanisms depends on
mobile phase content and pH, and as a consequence has the potential of selectivity modulation [1].
Analyses were performed on HPLC Thermo Acclaim Mixed Mode WCX-1 (3 μm, 2.1 x 150 mm)
column. During screening phase, factors of significant influence on cationic analytes behaviour were
determinated. For that reason, column temperature (30-38°C) and mobile phase composition
parameters (acetonitrile content (30-50% (v/v)), pH (3.8-5.6) and ionic strength (20-40 mM) of
aqueous part of mobile phase) were selected for optimization. Design of Experiments (DoE) was used
for simultaneous optimization of selected factors. Experimental plan was in line with face-centered
Central Composite Design. Optimization goals were set in order to adequately separate all critical
peak pairs, and execute the analysis in reasonable time. Since selectivity in mixed-mode HPLC can
be governed through mobile phase content, selectivity factor (α) values of critical peak pairs were set
as optimization goals (αBP/FT, αTH/BP, αLOF/DOX > 1.2). The retention factor of last eluting analyte (kDOX)
was desired not to be greater than 10, in order to assure the rational analysis time. Experimental plan
and mathematical models were obtained with Design-Expert 7.0.0 software. Obtained models were
statistically evaluated (R2, pred. R2 and adj. R2 > 0.99). The most pronounced effect on followed
responses had the organic solvent content, whose increase lead to αTH/BP
enhancing, and had the
opposite effect on αBP/FT, αLOF/DOX and kDOX. Higher ionic strength corresponded to better separation
of BP from both FT and TH. This can be assigned to competitive behaviour between analytes and
ions present in mobile phase [2]. Time analysis shortening resulted as a consequence of higher values
of organic solvent, ionic strength and temperature. However, mobile phase pH had the opposite effect,
which can be related to more expressed cationic interactions and greater retention of basic analytes
[2].
Taking into account effects of all factors, and according to generated Derringer’s desirability function
for multiobjective decision making, the values of the factors that give the optimal responses are
selected to be 44% of acetonitrile, ionic strength 36 mM, temperature of 38°C and mobile phase pH
of 5.1.
PB  - Aristotle University of Thessaloniki
PB  - National Technical University of Athens
C3  - IMA-2021, 12 International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event
T1  - Optimization of mixed-mode HPLC method intended for analysis of adrenergic drugs
SP  - 119
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4697
ER  - 

@conference{
author = "Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Zečević, Mira and Otašević, Biljana",
year = "2021",
abstract = "One of widely used drug group refers to drugs that act through adrenergic system. In following
research, the intent was to develop High Performance Liquid Chromatography (HPLC) method for
separation of adrenergic drugs. Therefore, selected mixture of analytes contained bisoprolol (BP),
fenoterole (FT), doxazosin (DOX), tetrahydrazoline (TH) and lofexidine (LOF). One of the
advantages of this method reflects in expanding knowledge about the analytical behaviour of
lofexidine, which is limited. Since all of selected analytes are basic in nature, mixed-mode column,
which includes reverse phase (RP) and weak cation exchange (WCX) interactions, was considered as
adequate for this HPLC analysis. The pronunciation one of two separation mechanisms depends on
mobile phase content and pH, and as a consequence has the potential of selectivity modulation [1].
Analyses were performed on HPLC Thermo Acclaim Mixed Mode WCX-1 (3 μm, 2.1 x 150 mm)
column. During screening phase, factors of significant influence on cationic analytes behaviour were
determinated. For that reason, column temperature (30-38°C) and mobile phase composition
parameters (acetonitrile content (30-50% (v/v)), pH (3.8-5.6) and ionic strength (20-40 mM) of
aqueous part of mobile phase) were selected for optimization. Design of Experiments (DoE) was used
for simultaneous optimization of selected factors. Experimental plan was in line with face-centered
Central Composite Design. Optimization goals were set in order to adequately separate all critical
peak pairs, and execute the analysis in reasonable time. Since selectivity in mixed-mode HPLC can
be governed through mobile phase content, selectivity factor (α) values of critical peak pairs were set
as optimization goals (αBP/FT, αTH/BP, αLOF/DOX > 1.2). The retention factor of last eluting analyte (kDOX)
was desired not to be greater than 10, in order to assure the rational analysis time. Experimental plan
and mathematical models were obtained with Design-Expert 7.0.0 software. Obtained models were
statistically evaluated (R2, pred. R2 and adj. R2 > 0.99). The most pronounced effect on followed
responses had the organic solvent content, whose increase lead to αTH/BP
enhancing, and had the
opposite effect on αBP/FT, αLOF/DOX and kDOX. Higher ionic strength corresponded to better separation
of BP from both FT and TH. This can be assigned to competitive behaviour between analytes and
ions present in mobile phase [2]. Time analysis shortening resulted as a consequence of higher values
of organic solvent, ionic strength and temperature. However, mobile phase pH had the opposite effect,
which can be related to more expressed cationic interactions and greater retention of basic analytes
[2].
Taking into account effects of all factors, and according to generated Derringer’s desirability function
for multiobjective decision making, the values of the factors that give the optimal responses are
selected to be 44% of acetonitrile, ionic strength 36 mM, temperature of 38°C and mobile phase pH
of 5.1.",
publisher = "Aristotle University of Thessaloniki, National Technical University of Athens",
journal = "IMA-2021, 12 International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event",
title = "Optimization of mixed-mode HPLC method intended for analysis of adrenergic drugs",
pages = "119-119",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4697"
}

Svrkota, B., Krmar, J., Protić, A., Zečević, M.,& Otašević, B.. (2021). Optimization of mixed-mode HPLC method intended for analysis of adrenergic drugs. in IMA-2021, 12 International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event
Aristotle University of Thessaloniki., 119-119.
https://hdl.handle.net/21.15107/rcub_farfar_4697

Svrkota B, Krmar J, Protić A, Zečević M, Otašević B. Optimization of mixed-mode HPLC method intended for analysis of adrenergic drugs. in IMA-2021, 12 International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event. 2021;:119-119.
https://hdl.handle.net/21.15107/rcub_farfar_4697 .

Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Zečević, Mira, Otašević, Biljana, "Optimization of mixed-mode HPLC method intended for analysis of adrenergic drugs" in IMA-2021, 12 International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event (2021):119-119,
https://hdl.handle.net/21.15107/rcub_farfar_4697 .

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 . .

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 . .

TY  - CONF
AU  - Otašević, Biljana
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Zečević, Mira
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4693
AB  - Liquid chromatography system in which several separation mechanisms are integrated in the
composition of a single column is called multimodal or mixed-mode chromatography (MMC). MMC
systems are classified based on combined separation mechanisms as bimodal (RP/HILIC, RP/IEX,
HILIC/IEX) and trimodal (different combinations of RP/HILIC/IEX). The main benefit of MMC lies
in widening the spectra of properties of analytes that can be simultaneously chromatographed
(nonpolar, polar, organic, inorganic, ionized and / or non-ionized analytes). In this way, it is possible
to reduce the number of required analyses for one complex sample compared to unimodal
chromatographic systems. For that reason, the popularity of MMC has been growing fast in recent
years. However, in line with this achievement, MMC is characterized by large number of
intermolecular interactions governing separations which are related to the properties of the analyte
(charge and polarity) and chromatographic conditions (ionic strength and the pH of the aqueous phase
and the content of the organic solvent) [1]. In order to get insight into relative contribution of
aforementioned factors to retention of selected group of analytes, preferred chemometric approach is
Quantitative Structure Retention Relationship (QSRR) study. The QSRR models relate the physicalchemical
properties of analytes reflected by assigned molecular descriptors with their retention
behaviour in predefined experimental space described by the range of chromatographic conditions
(instrumental and mobile phase composition related factors). Apart from its general purpose to assist
in the characterization of observed chromatographic system, the reliable predictions of retention
behaviour of so-called system blind analytes (analytes of known chemical structure but not subjected
to experimentations) can also be derived from a QSRR model. In such way, the development of MMC
based analytical method can be rationalized by saving time and other resources [2].
This research demonstrates the QSRR study performed on 31 pharmaceuticals covering wide range
of polarities, acid-base properties and divergent retention in RP/WCX system (Thermo Acclaim
Mixed Mode WCX-1 3 μm, 2.1x150 mm column). This system was subjected to variations of the
mobile phase composition (30-50% (v/v) of acetonitrile; 3.8-5.6 pH value and 20-40 mM ionic
strength of acetic buffer) and column temperature (30–38 °C) according to the plan of central
composite design of experiments. The machine learning algorithm based on Artificial Neural
Network was used for relating these independent variables to cube root transformed retention factors
of analytes as observed responses. The network comprising of 11-7-1 topology was trained through
1200 cycles with learning rate set at 0.3 and momentum set at 0.5. Cross validation and external
validation were used to prove good statistical performances of built model (Root Mean Square Error
values 0.131 and 0.147 and Squared Correlation vales 0.963 and 0.944, respectively). According to
the weighting scheme used, volume fraction of acetonitrile, pH of aqueous phase and descriptors
related to hydrophobicity and molecule size demonstrated the greatest impact towards retention in
MMC.
PB  - Aristotle University of Thessaloniki
PB  - National Technical University of Athens
C3  - 12th International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event
T1  - QSRR driven insight into retention in multimodal chromatography
SP  - 50
EP  - 50
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4693
ER  - 

@conference{
author = "Otašević, Biljana and Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Zečević, Mira",
year = "2021",
abstract = "Liquid chromatography system in which several separation mechanisms are integrated in the
composition of a single column is called multimodal or mixed-mode chromatography (MMC). MMC
systems are classified based on combined separation mechanisms as bimodal (RP/HILIC, RP/IEX,
HILIC/IEX) and trimodal (different combinations of RP/HILIC/IEX). The main benefit of MMC lies
in widening the spectra of properties of analytes that can be simultaneously chromatographed
(nonpolar, polar, organic, inorganic, ionized and / or non-ionized analytes). In this way, it is possible
to reduce the number of required analyses for one complex sample compared to unimodal
chromatographic systems. For that reason, the popularity of MMC has been growing fast in recent
years. However, in line with this achievement, MMC is characterized by large number of
intermolecular interactions governing separations which are related to the properties of the analyte
(charge and polarity) and chromatographic conditions (ionic strength and the pH of the aqueous phase
and the content of the organic solvent) [1]. In order to get insight into relative contribution of
aforementioned factors to retention of selected group of analytes, preferred chemometric approach is
Quantitative Structure Retention Relationship (QSRR) study. The QSRR models relate the physicalchemical
properties of analytes reflected by assigned molecular descriptors with their retention
behaviour in predefined experimental space described by the range of chromatographic conditions
(instrumental and mobile phase composition related factors). Apart from its general purpose to assist
in the characterization of observed chromatographic system, the reliable predictions of retention
behaviour of so-called system blind analytes (analytes of known chemical structure but not subjected
to experimentations) can also be derived from a QSRR model. In such way, the development of MMC
based analytical method can be rationalized by saving time and other resources [2].
This research demonstrates the QSRR study performed on 31 pharmaceuticals covering wide range
of polarities, acid-base properties and divergent retention in RP/WCX system (Thermo Acclaim
Mixed Mode WCX-1 3 μm, 2.1x150 mm column). This system was subjected to variations of the
mobile phase composition (30-50% (v/v) of acetonitrile; 3.8-5.6 pH value and 20-40 mM ionic
strength of acetic buffer) and column temperature (30–38 °C) according to the plan of central
composite design of experiments. The machine learning algorithm based on Artificial Neural
Network was used for relating these independent variables to cube root transformed retention factors
of analytes as observed responses. The network comprising of 11-7-1 topology was trained through
1200 cycles with learning rate set at 0.3 and momentum set at 0.5. Cross validation and external
validation were used to prove good statistical performances of built model (Root Mean Square Error
values 0.131 and 0.147 and Squared Correlation vales 0.963 and 0.944, respectively). According to
the weighting scheme used, volume fraction of acetonitrile, pH of aqueous phase and descriptors
related to hydrophobicity and molecule size demonstrated the greatest impact towards retention in
MMC.",
publisher = "Aristotle University of Thessaloniki, National Technical University of Athens",
journal = "12th International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event",
title = "QSRR driven insight into retention in multimodal chromatography",
pages = "50-50",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4693"
}

Otašević, B., Svrkota, B., Krmar, J., Protić, A.,& Zečević, M.. (2021). QSRR driven insight into retention in multimodal chromatography. in 12th International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event
Aristotle University of Thessaloniki., 50-50.
https://hdl.handle.net/21.15107/rcub_farfar_4693

Otašević B, Svrkota B, Krmar J, Protić A, Zečević M. QSRR driven insight into retention in multimodal chromatography. in 12th International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event. 2021;:50-50.
https://hdl.handle.net/21.15107/rcub_farfar_4693 .

Otašević, Biljana, Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Zečević, Mira, "QSRR driven insight into retention in multimodal chromatography" in 12th International Conference on Instrumental Methods of Analysis, Modern Trends and Applications, 20-23 September 2021, Virtual event (2021):50-50,
https://hdl.handle.net/21.15107/rcub_farfar_4693 .

TY  - JOUR
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Đajić, Nevena
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4902
AB  - In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated
for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to
decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity
was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on
BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting
of acetonitrile and 20mmol/L ammonium-acetate solution in different ratios. Retention data
was used to derivatize the lipophilicity estimates logkw, S and u0: Computational substructurebased
and property-based methods were employed to calculate the logP, logD, milogP, AlogP,
XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing
hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly
evaluate the prediction ability of each method. This test unambiguously recognized SðC18Þ, AlogP
and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound
denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL
PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development.
PB  - Taylor & Francis Inc.
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Chromatographic and computational lipophilicity assessment of novel antibiofilm agents
VL  - 43
IS  - 15-16
SP  - 615
EP  - 623
DO  - 10.1080/10826076.2020.1777154
ER  - 

@article{
author = "Krmar, Jovana and Protić, Ana and Đajić, Nevena and Zečević, Mira and Otašević, Biljana",
year = "2020",
abstract = "In this study, lipophilicity of five newly designed molecules with antibiofilm properties was estimated
for the first time. The overall goal of lipophilicity evaluation in lead generation phase is to
decrease the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity
was assessed using RP-HPLC and in silico methods. Chromatographic analyses were performed on
BDS Thermo Scientific Hypersil C18 and Phenomenex Kinetex C8 columns with mobile phase consisting
of acetonitrile and 20mmol/L ammonium-acetate solution in different ratios. Retention data
was used to derivatize the lipophilicity estimates logkw, S and u0: Computational substructurebased
and property-based methods were employed to calculate the logP, logD, milogP, AlogP,
XlogP2, XlogP3, AlogPs, AClogP and MlogP descriptors. Due to the incongruent trends of increasing
hydrophobicity observed among the scales, the Sum of Ranking Differences was used to fairly
evaluate the prediction ability of each method. This test unambiguously recognized SðC18Þ, AlogP
and XlogP2 as the best lipophilicity measures. By virtue of the respective scales, compound
denoted as DIRL PIP was identified as the most lipophilic one. Out of concern related to the DIRL
PIP’s anticipated toxicity, less hydrophobic MHK 9a should be subjected to the further drug development.",
publisher = "Taylor & Francis Inc.",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Chromatographic and computational lipophilicity assessment of novel antibiofilm agents",
volume = "43",
number = "15-16",
pages = "615-623",
doi = "10.1080/10826076.2020.1777154"
}

Krmar, J., Protić, A., Đajić, N., Zečević, M.,& Otašević, B.. (2020). Chromatographic and computational lipophilicity assessment of novel antibiofilm agents. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc.., 43(15-16), 615-623.
https://doi.org/10.1080/10826076.2020.1777154

Krmar J, Protić A, Đajić N, Zečević M, Otašević B. Chromatographic and computational lipophilicity assessment of novel antibiofilm agents. in Journal of Liquid Chromatography & Related Technologies. 2020;43(15-16):615-623.
doi:10.1080/10826076.2020.1777154 .

Krmar, Jovana, Protić, Ana, Đajić, Nevena, Zečević, Mira, Otašević, Biljana, "Chromatographic and computational lipophilicity assessment of novel antibiofilm agents" in Journal of Liquid Chromatography & Related Technologies, 43, no. 15-16 (2020):615-623,
https://doi.org/10.1080/10826076.2020.1777154 . .

TY  - JOUR
AU  - Mitrović, Marija
AU  - Protić, Ana
AU  - Malenović, Anđelija
AU  - Otašević, Biljana
AU  - Zečević, Mira
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3483
AB  - Official method in Ph. Eur. for evaluation of timolol enantiomeric purity is normal-phase high perfor-mance liquid chromatography (NP-HPLC) method. Compared to other HPLC modes, NP is depicted asquite expensive with high consumption of organic solvents which leads to chronic exposure of analyststo toxic and carcinogenic effects. In order to overcome above-mentioned drawbacks, the aim of thisstudy was to develop new method with better eco-friendly features. This was enabled by using proteintype Chiral Stationary Phase (CSP) in reversed-phase mode that required up to 10 % (v/v) of organicsolvent. Therefore, an enantioselective HPLC method was developed and validated for quantification of(S)-timolol and its chiral impurity, (R)-isomer. Optimized separation conditions on ovomucoid columnwere set using Analytical Quality by Design (AQbD) approach in method development. Optimizationstep was performed following the Box-Behnken experimental plan and the influence of three criticalmethod parameters (CMPs) towards enantioseparation of the above-mentioned peak pair was exam-ined. CMPs included variation of acetonitrile content in the mobile phase (5–10 %, v/v), pH value of theaqueous phase (6.0–7.0) and ammonium chloride concentration in the aqueous part of the mobile phase(10−30 mmol L−1). The most relevant critical method attributes (CMAs) in this case were the separa-tion criterion between studied critical pair and retention factor of the second eluting peak, (S)-timolol.Qualitative Design Space (DS) was defined by Monte Carlo simulations providing adequate assurance ofmethod’s qualitative robustness ( = 95 %). The selected working point situated in the middle of the DSwas characterized by following combination of CMPs: acetonitrile content in the mobile phase 7 % (v/v),pH value of the aqueous phase 6.8 and concentration of ammonium chloride in aqueous phase 14 mmolL–1. In the next step, the quantitative robustness was tested by Plackett-Burman experimental design. Thevalidation studies confirmed adequacy of the proposed method for its intended purpose. Finally, Ana-lytical Eco-Scale metric tool was applied to confirm that developed method represents excellent greenanalytical method compared to the official one.
PB  - Elsevier
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase
VL  - 180
DO  - 10.1016/j.jpba.2019.113034
ER  - 

@article{
author = "Mitrović, Marija and Protić, Ana and Malenović, Anđelija and Otašević, Biljana and Zečević, Mira",
year = "2020",
abstract = "Official method in Ph. Eur. for evaluation of timolol enantiomeric purity is normal-phase high perfor-mance liquid chromatography (NP-HPLC) method. Compared to other HPLC modes, NP is depicted asquite expensive with high consumption of organic solvents which leads to chronic exposure of analyststo toxic and carcinogenic effects. In order to overcome above-mentioned drawbacks, the aim of thisstudy was to develop new method with better eco-friendly features. This was enabled by using proteintype Chiral Stationary Phase (CSP) in reversed-phase mode that required up to 10 % (v/v) of organicsolvent. Therefore, an enantioselective HPLC method was developed and validated for quantification of(S)-timolol and its chiral impurity, (R)-isomer. Optimized separation conditions on ovomucoid columnwere set using Analytical Quality by Design (AQbD) approach in method development. Optimizationstep was performed following the Box-Behnken experimental plan and the influence of three criticalmethod parameters (CMPs) towards enantioseparation of the above-mentioned peak pair was exam-ined. CMPs included variation of acetonitrile content in the mobile phase (5–10 %, v/v), pH value of theaqueous phase (6.0–7.0) and ammonium chloride concentration in the aqueous part of the mobile phase(10−30 mmol L−1). The most relevant critical method attributes (CMAs) in this case were the separa-tion criterion between studied critical pair and retention factor of the second eluting peak, (S)-timolol.Qualitative Design Space (DS) was defined by Monte Carlo simulations providing adequate assurance ofmethod’s qualitative robustness ( = 95 %). The selected working point situated in the middle of the DSwas characterized by following combination of CMPs: acetonitrile content in the mobile phase 7 % (v/v),pH value of the aqueous phase 6.8 and concentration of ammonium chloride in aqueous phase 14 mmolL–1. In the next step, the quantitative robustness was tested by Plackett-Burman experimental design. Thevalidation studies confirmed adequacy of the proposed method for its intended purpose. Finally, Ana-lytical Eco-Scale metric tool was applied to confirm that developed method represents excellent greenanalytical method compared to the official one.",
publisher = "Elsevier",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase",
volume = "180",
doi = "10.1016/j.jpba.2019.113034"
}

Mitrović, M., Protić, A., Malenović, A., Otašević, B.,& Zečević, M.. (2020). Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier., 180.
https://doi.org/10.1016/j.jpba.2019.113034

Mitrović M, Protić A, Malenović A, Otašević B, Zečević M. Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase. in Journal of Pharmaceutical and Biomedical Analysis. 2020;180.
doi:10.1016/j.jpba.2019.113034 .

Mitrović, Marija, Protić, Ana, Malenović, Anđelija, Otašević, Biljana, Zečević, Mira, "Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase" in Journal of Pharmaceutical and Biomedical Analysis, 180 (2020),
https://doi.org/10.1016/j.jpba.2019.113034 . .

TY  - CONF
AU  - Protić, Ana
AU  - Maljurić, Nevena
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Zečević, Mira
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4705
PB  - BIOSCOPE Research Group | PROTEOMASS Scientific Society
C3  - 4th International Caparica Christmas Conference on Sample Treatement, 30th November - 3rd December 2020, Caparica, Portugal (on-line), 2020.
T1  - Significant molecular and complex association descriptors in QSRR modelling of Green Liquid Chromatography using β-cyclodextrin mobile phases
SP  - 94
EP  - 94
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4705
ER  - 

@conference{
author = "Protić, Ana and Maljurić, Nevena and Otašević, Biljana and Malenović, Anđelija and Zečević, Mira",
year = "2020",
publisher = "BIOSCOPE Research Group | PROTEOMASS Scientific Society",
journal = "4th International Caparica Christmas Conference on Sample Treatement, 30th November - 3rd December 2020, Caparica, Portugal (on-line), 2020.",
title = "Significant molecular and complex association descriptors in QSRR modelling of Green Liquid Chromatography using β-cyclodextrin mobile phases",
pages = "94-94",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4705"
}

Protić, A., Maljurić, N., Otašević, B., Malenović, A.,& Zečević, M.. (2020). Significant molecular and complex association descriptors in QSRR modelling of Green Liquid Chromatography using β-cyclodextrin mobile phases. in 4th International Caparica Christmas Conference on Sample Treatement, 30th November - 3rd December 2020, Caparica, Portugal (on-line), 2020.
BIOSCOPE Research Group | PROTEOMASS Scientific Society., 94-94.
https://hdl.handle.net/21.15107/rcub_farfar_4705

Protić A, Maljurić N, Otašević B, Malenović A, Zečević M. Significant molecular and complex association descriptors in QSRR modelling of Green Liquid Chromatography using β-cyclodextrin mobile phases. in 4th International Caparica Christmas Conference on Sample Treatement, 30th November - 3rd December 2020, Caparica, Portugal (on-line), 2020.. 2020;:94-94.
https://hdl.handle.net/21.15107/rcub_farfar_4705 .

Protić, Ana, Maljurić, Nevena, Otašević, Biljana, Malenović, Anđelija, Zečević, Mira, "Significant molecular and complex association descriptors in QSRR modelling of Green Liquid Chromatography using β-cyclodextrin mobile phases" in 4th International Caparica Christmas Conference on Sample Treatement, 30th November - 3rd December 2020, Caparica, Portugal (on-line), 2020. (2020):94-94,
https://hdl.handle.net/21.15107/rcub_farfar_4705 .

TY  - JOUR
AU  - Krmar, Jovana
AU  - Vukićević, Milan
AU  - Kovačević, Ana
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3585
AB  - In micellar liquid chromatography (MLC), the addition of a surfactant to the mobile phase in excess is accompanied by an alteration of its solubilising capacity and a change in the stationary phase’s properties. As an implication, the prediction of the analytes’ retention in MLC mode becomes a challenging task. Mixed Quantitative Structure –Retention Relationships (QSRR) modelling represents a powerful tool for estimating the analytes’ retention. This study compares 48 successfully developed mixed QSRR models with respect to their ability to predict retention of aripiprazole and its five impurities from molecular structures and factors that de- scribe the Brij - acetonitrile system. The development of the models was based on an automatic com- bining of six attribute (feature) selection methods with eight predictive algorithms and the optimiza- tion of hyper-parameters. The feature selection methods included Principal Component Analysis (PCA), Non-negative Matrix Factorization (NMF), ReliefF, Multiple Linear Regression (MLR), Mutual Info and F- Regression. The series of investigated predictive algorithms comprised Linear Regressions (LR), Ridge Re- gression, Lasso Regression, Artificial Neural Networks (ANN), Support Vector Regression (SVR), Random Forest (RF), Gradient Boosted Trees (GBT) and K-Nearest neighbourhood (k-NN). A sufficient amount of data for building the model (78 cases in total) was provided by conducting 13 experiments for each of the 6 analytes and collecting the target responses afterwards. Different experi- mental settings were established by varying the values of the concentration of Brij L23, pH of the aqueous phase and acetonitrile content in the mobile phase according to the Box-Behnken design. In addition to the chromatographic parameters, the pool of independent variables was expanded by 27 molecular de- scriptors from all major groups (physicochemical, quantum chemical, topological and spatial structural descriptors). The best model was chosen by taking into consideration the Root Mean Square Error ( RMSE ) and cross-validation (CV) correlation coefficient ( Q 2 ) values. Interestingly, the comparative analysis indicated that a change in the set of input variables had a minor impact on the performance of the final models. On the other hand, different regression algorithms showed great diversity in the ability to learn patterns conserved in the data. In this regard, testing many regression algorithms is necessary in order to find the most suitable technique for model building. In the specific case, GBT-based models have demonstrated the best ability to predict the retention factor in the MLC mode. Steric factors and dipole-dipole interactions have proven to be relevant to the observed retention behaviour. This study, although being of a smaller scale, is a most promising starting point for comprehensive MLC retention prediction.
PB  - Elsevier
T2  - Journal of Chromatography A
T1  - Performance comparison of nonlinear and linear regression algorithms coupled with different attribute selection methods for quantitative structure - retention relationships modelling in micellar liquid chromatography
VL  - 1623
DO  - 10.1016/j.chroma.2020.461146
ER  - 

@article{
author = "Krmar, Jovana and Vukićević, Milan and Kovačević, Ana and Protić, Ana and Zečević, Mira and Otašević, Biljana",
year = "2020",
abstract = "In micellar liquid chromatography (MLC), the addition of a surfactant to the mobile phase in excess is accompanied by an alteration of its solubilising capacity and a change in the stationary phase’s properties. As an implication, the prediction of the analytes’ retention in MLC mode becomes a challenging task. Mixed Quantitative Structure –Retention Relationships (QSRR) modelling represents a powerful tool for estimating the analytes’ retention. This study compares 48 successfully developed mixed QSRR models with respect to their ability to predict retention of aripiprazole and its five impurities from molecular structures and factors that de- scribe the Brij - acetonitrile system. The development of the models was based on an automatic com- bining of six attribute (feature) selection methods with eight predictive algorithms and the optimiza- tion of hyper-parameters. The feature selection methods included Principal Component Analysis (PCA), Non-negative Matrix Factorization (NMF), ReliefF, Multiple Linear Regression (MLR), Mutual Info and F- Regression. The series of investigated predictive algorithms comprised Linear Regressions (LR), Ridge Re- gression, Lasso Regression, Artificial Neural Networks (ANN), Support Vector Regression (SVR), Random Forest (RF), Gradient Boosted Trees (GBT) and K-Nearest neighbourhood (k-NN). A sufficient amount of data for building the model (78 cases in total) was provided by conducting 13 experiments for each of the 6 analytes and collecting the target responses afterwards. Different experi- mental settings were established by varying the values of the concentration of Brij L23, pH of the aqueous phase and acetonitrile content in the mobile phase according to the Box-Behnken design. In addition to the chromatographic parameters, the pool of independent variables was expanded by 27 molecular de- scriptors from all major groups (physicochemical, quantum chemical, topological and spatial structural descriptors). The best model was chosen by taking into consideration the Root Mean Square Error ( RMSE ) and cross-validation (CV) correlation coefficient ( Q 2 ) values. Interestingly, the comparative analysis indicated that a change in the set of input variables had a minor impact on the performance of the final models. On the other hand, different regression algorithms showed great diversity in the ability to learn patterns conserved in the data. In this regard, testing many regression algorithms is necessary in order to find the most suitable technique for model building. In the specific case, GBT-based models have demonstrated the best ability to predict the retention factor in the MLC mode. Steric factors and dipole-dipole interactions have proven to be relevant to the observed retention behaviour. This study, although being of a smaller scale, is a most promising starting point for comprehensive MLC retention prediction.",
publisher = "Elsevier",
journal = "Journal of Chromatography A",
title = "Performance comparison of nonlinear and linear regression algorithms coupled with different attribute selection methods for quantitative structure - retention relationships modelling in micellar liquid chromatography",
volume = "1623",
doi = "10.1016/j.chroma.2020.461146"
}

Krmar, J., Vukićević, M., Kovačević, A., Protić, A., Zečević, M.,& Otašević, B.. (2020). Performance comparison of nonlinear and linear regression algorithms coupled with different attribute selection methods for quantitative structure - retention relationships modelling in micellar liquid chromatography. in Journal of Chromatography A
Elsevier., 1623.
https://doi.org/10.1016/j.chroma.2020.461146

Krmar J, Vukićević M, Kovačević A, Protić A, Zečević M, Otašević B. Performance comparison of nonlinear and linear regression algorithms coupled with different attribute selection methods for quantitative structure - retention relationships modelling in micellar liquid chromatography. in Journal of Chromatography A. 2020;1623.
doi:10.1016/j.chroma.2020.461146 .

Krmar, Jovana, Vukićević, Milan, Kovačević, Ana, Protić, Ana, Zečević, Mira, Otašević, Biljana, "Performance comparison of nonlinear and linear regression algorithms coupled with different attribute selection methods for quantitative structure - retention relationships modelling in micellar liquid chromatography" in Journal of Chromatography A, 1623 (2020),
https://doi.org/10.1016/j.chroma.2020.461146 . .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Otašević, Biljana
AU  - Golubović, Jelena
AU  - Krmar, Jovana
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3512
AB  - Green analytical chemistry is primarily directed towards minimization of the amount of waste associated with either the sample preparation or analysis. Among different chromatographic methods, liquid chromatography is considered the least green, allowing for various possibilities for greening. Using green solvents such as ethanol or acetone in RP-HPLC, as an alternative to acetonitrile, is recently attracting an attention. Both ethanol and acetone are characterized with low toxicity, with certain drawbacks limiting their regular use in RP-HPLC. Ethanol has low eluotropic strength and causes high backpressures, while acetone shows high UV cut-off, making it unsuitable for UV/Vis detection. To overcome the existing problems, Corona Charged Aerosol Detector was employed for development of RP-HPLC methods for separation of risperidone and its structurally related impurities with either ethanol or acetone as organic modifier. The methods were optimized by experimental design methodology, while optimal conditions for separation were determined using Derringer's desirability function. Detailed assessment of 3D surface plots of Derringer's desirability function enabled selection of 0.6 mL min−1 flow rate and 20% (v/v) organic modifier content as optimal when using ethanol, while in case of acetone mobile phase flow rate was 0.8 mL min−1 and organic modifier content 17% (v/v). Methods were validated and their eco-friendly character was confirmed through Green Analytical Procedure Index (GAPI). Although both methods are ecologically acceptable, the main drawback is reflected in the fact that no recycling or another waste treatment method exist. In the end, acetone was prioritized over ethanol, due to lower health hazard and decreased amount of generated waste.
PB  - Elsevier
T2  - Microchemical Journal
T1  - A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities
VL  - 153
DO  - 10.1016/j.microc.2019.104394
ER  - 

@article{
author = "Maljurić, Nevena and Otašević, Biljana and Golubović, Jelena and Krmar, Jovana and Zečević, Mira and Protić, Ana",
year = "2020",
abstract = "Green analytical chemistry is primarily directed towards minimization of the amount of waste associated with either the sample preparation or analysis. Among different chromatographic methods, liquid chromatography is considered the least green, allowing for various possibilities for greening. Using green solvents such as ethanol or acetone in RP-HPLC, as an alternative to acetonitrile, is recently attracting an attention. Both ethanol and acetone are characterized with low toxicity, with certain drawbacks limiting their regular use in RP-HPLC. Ethanol has low eluotropic strength and causes high backpressures, while acetone shows high UV cut-off, making it unsuitable for UV/Vis detection. To overcome the existing problems, Corona Charged Aerosol Detector was employed for development of RP-HPLC methods for separation of risperidone and its structurally related impurities with either ethanol or acetone as organic modifier. The methods were optimized by experimental design methodology, while optimal conditions for separation were determined using Derringer's desirability function. Detailed assessment of 3D surface plots of Derringer's desirability function enabled selection of 0.6 mL min−1 flow rate and 20% (v/v) organic modifier content as optimal when using ethanol, while in case of acetone mobile phase flow rate was 0.8 mL min−1 and organic modifier content 17% (v/v). Methods were validated and their eco-friendly character was confirmed through Green Analytical Procedure Index (GAPI). Although both methods are ecologically acceptable, the main drawback is reflected in the fact that no recycling or another waste treatment method exist. In the end, acetone was prioritized over ethanol, due to lower health hazard and decreased amount of generated waste.",
publisher = "Elsevier",
journal = "Microchemical Journal",
title = "A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities",
volume = "153",
doi = "10.1016/j.microc.2019.104394"
}

Maljurić, N., Otašević, B., Golubović, J., Krmar, J., Zečević, M.,& Protić, A.. (2020). A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities. in Microchemical Journal
Elsevier., 153.
https://doi.org/10.1016/j.microc.2019.104394

Maljurić N, Otašević B, Golubović J, Krmar J, Zečević M, Protić A. A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities. in Microchemical Journal. 2020;153.
doi:10.1016/j.microc.2019.104394 .

Maljurić, Nevena, Otašević, Biljana, Golubović, Jelena, Krmar, Jovana, Zečević, Mira, Protić, Ana, "A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities" in Microchemical Journal, 153 (2020),
https://doi.org/10.1016/j.microc.2019.104394 . .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3557
AB  - When cyclodextrins (CDs) are used in chromatography analytes’ retention time is decreased with an in- crease in concentration of CD in the mobile phase. Thus complex stability constants can be determined from the change in retention time of the ligand molecule upon complexation. Since the preceding ap- proach implies extensive and time-consuming HPLC experiments, the goal of this research was to inves- tigate the possibility of using in silico prediction tools instead. Quantitative structure–retention relation- ship (QSRR) model previously developed to explain the retention behavior of risperidone, olanzapine and their structurally related impurities in β-CD modified HPLC system was applied to predict retention fac- tor under different chromatographic conditions within the examined domains. Predicted retention factors were further used for calculation of stability constants and important thermodynamic parameters, namely standard Gibbs free energy, standard molar enthalpy and entropy, contributing to inclusion phenomenon. Unexpected prolonged retention with an increase in β-CD concentration was observed, in contrast to the employed chromatographic theory used for the calculation of the stability constants. Consequently, it led to failure in stability constants and thermodynamic parameters calculation for almost all analytes when acetonitrile content was 20% (v/v) across the investigated pH range. Moreover, ionization of investigated analytes and free stationary phase silanol groups are pH dependent, leading to minimization of secondary interactions if free silanol groups are non-ionized at pH lower than 3. In order to prove accuracy of pre- dicted retention factors, HPLC verification experiments were performed and good agreement between predicted and experimental values was obtained, confirming the applicability of proposed in-silico tool. However, the obtained results opened some novel questions and revealed that chromatographic method is not overall applicable in calculation of stability constants and thermodynamic parameters indicating the complexity of β-CD modified systems.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process
VL  - 1619
DO  - 10.1016/j.chroma.2020.460971
ER  - 

@article{
author = "Maljurić, Nevena and Otašević, Biljana and Malenović, Anđelija and Zečević, Mira and Protić, Ana",
year = "2020",
abstract = "When cyclodextrins (CDs) are used in chromatography analytes’ retention time is decreased with an in- crease in concentration of CD in the mobile phase. Thus complex stability constants can be determined from the change in retention time of the ligand molecule upon complexation. Since the preceding ap- proach implies extensive and time-consuming HPLC experiments, the goal of this research was to inves- tigate the possibility of using in silico prediction tools instead. Quantitative structure–retention relation- ship (QSRR) model previously developed to explain the retention behavior of risperidone, olanzapine and their structurally related impurities in β-CD modified HPLC system was applied to predict retention fac- tor under different chromatographic conditions within the examined domains. Predicted retention factors were further used for calculation of stability constants and important thermodynamic parameters, namely standard Gibbs free energy, standard molar enthalpy and entropy, contributing to inclusion phenomenon. Unexpected prolonged retention with an increase in β-CD concentration was observed, in contrast to the employed chromatographic theory used for the calculation of the stability constants. Consequently, it led to failure in stability constants and thermodynamic parameters calculation for almost all analytes when acetonitrile content was 20% (v/v) across the investigated pH range. Moreover, ionization of investigated analytes and free stationary phase silanol groups are pH dependent, leading to minimization of secondary interactions if free silanol groups are non-ionized at pH lower than 3. In order to prove accuracy of pre- dicted retention factors, HPLC verification experiments were performed and good agreement between predicted and experimental values was obtained, confirming the applicability of proposed in-silico tool. However, the obtained results opened some novel questions and revealed that chromatographic method is not overall applicable in calculation of stability constants and thermodynamic parameters indicating the complexity of β-CD modified systems.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process",
volume = "1619",
doi = "10.1016/j.chroma.2020.460971"
}

Maljurić, N., Otašević, B., Malenović, A., Zečević, M.,& Protić, A.. (2020). Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process. in Journal of Chromatography A
Elsevier B.V.., 1619.
https://doi.org/10.1016/j.chroma.2020.460971

Maljurić N, Otašević B, Malenović A, Zečević M, Protić A. Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process. in Journal of Chromatography A. 2020;1619.
doi:10.1016/j.chroma.2020.460971 .

Maljurić, Nevena, Otašević, Biljana, Malenović, Anđelija, Zečević, Mira, Protić, Ana, "Quantitative structure retention relationship modeling as potential tool in chromatographic determination of stability constants and thermodynamic parameters of β-cyclodextrin complexation process" in Journal of Chromatography A, 1619 (2020),
https://doi.org/10.1016/j.chroma.2020.460971 . .

TY  - CONF
AU  - Mitrović, Marija
AU  - Malenović, Anđelija
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Zečević, Mira
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4706
PB  - University of Milano-Bicocca
C3  - 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
T1  - Development and validation of a HPLC method for the enantiomeric purity testing of timolol maleate on ovomucoid chiral stationary phase
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4706
ER  - 

@conference{
author = "Mitrović, Marija and Malenović, Anđelija and Otašević, Biljana and Protić, Ana and Zečević, Mira",
year = "2019",
publisher = "University of Milano-Bicocca",
journal = "48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.",
title = "Development and validation of a HPLC method for the enantiomeric purity testing of timolol maleate on ovomucoid chiral stationary phase",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4706"
}

Mitrović, M., Malenović, A., Otašević, B., Protić, A.,& Zečević, M.. (2019). Development and validation of a HPLC method for the enantiomeric purity testing of timolol maleate on ovomucoid chiral stationary phase. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
University of Milano-Bicocca..
https://hdl.handle.net/21.15107/rcub_farfar_4706

Mitrović M, Malenović A, Otašević B, Protić A, Zečević M. Development and validation of a HPLC method for the enantiomeric purity testing of timolol maleate on ovomucoid chiral stationary phase. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_4706 .

Mitrović, Marija, Malenović, Anđelija, Otašević, Biljana, Protić, Ana, Zečević, Mira, "Development and validation of a HPLC method for the enantiomeric purity testing of timolol maleate on ovomucoid chiral stationary phase" in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy. (2019),
https://hdl.handle.net/21.15107/rcub_farfar_4706 .

TY  - CONF
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Đajić, Nevena
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4704
PB  - MSBM
C3  - XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
T1  - Predicting APCI Signal Intensities of Diverse Antipsychotics by Mixed QSPR Models and Comparison of Their Generalization Performances
SP  - 36
EP  - 36
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4704
ER  - 

@conference{
author = "Krmar, Jovana and Protić, Ana and Đajić, Nevena and Zečević, Mira and Otašević, Biljana",
year = "2019",
publisher = "MSBM",
journal = "XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.",
title = "Predicting APCI Signal Intensities of Diverse Antipsychotics by Mixed QSPR Models and Comparison of Their Generalization Performances",
pages = "36-36",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4704"
}

Krmar, J., Protić, A., Đajić, N., Zečević, M.,& Otašević, B.. (2019). Predicting APCI Signal Intensities of Diverse Antipsychotics by Mixed QSPR Models and Comparison of Their Generalization Performances. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
MSBM., 36-36.
https://hdl.handle.net/21.15107/rcub_farfar_4704

Krmar J, Protić A, Đajić N, Zečević M, Otašević B. Predicting APCI Signal Intensities of Diverse Antipsychotics by Mixed QSPR Models and Comparison of Their Generalization Performances. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.. 2019;:36-36.
https://hdl.handle.net/21.15107/rcub_farfar_4704 .

Krmar, Jovana, Protić, Ana, Đajić, Nevena, Zečević, Mira, Otašević, Biljana, "Predicting APCI Signal Intensities of Diverse Antipsychotics by Mixed QSPR Models and Comparison of Their Generalization Performances" in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia. (2019):36-36,
https://hdl.handle.net/21.15107/rcub_farfar_4704 .

TY  - CONF
AU  - Krmar, Jovana
AU  - Stojković, Jovana
AU  - Džigal, Merima
AU  - Protić, Ana
AU  - Maljurić, Nevena
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4708
PB  - University of Milano-Bicocca
C3  - 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
T1  - Modeling the impact of experimental parameters and molecular structures on APCI signalsʼ intensities of selected antipsychotics using gradient boosted trees
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4708
ER  - 

@conference{
author = "Krmar, Jovana and Stojković, Jovana and Džigal, Merima and Protić, Ana and Maljurić, Nevena and Zečević, Mira and Otašević, Biljana",
year = "2019",
publisher = "University of Milano-Bicocca",
journal = "48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.",
title = "Modeling the impact of experimental parameters and molecular structures on APCI signalsʼ intensities of selected antipsychotics using gradient boosted trees",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4708"
}

Krmar, J., Stojković, J., Džigal, M., Protić, A., Maljurić, N., Zečević, M.,& Otašević, B.. (2019). Modeling the impact of experimental parameters and molecular structures on APCI signalsʼ intensities of selected antipsychotics using gradient boosted trees. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
University of Milano-Bicocca..
https://hdl.handle.net/21.15107/rcub_farfar_4708

Krmar J, Stojković J, Džigal M, Protić A, Maljurić N, Zečević M, Otašević B. Modeling the impact of experimental parameters and molecular structures on APCI signalsʼ intensities of selected antipsychotics using gradient boosted trees. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_4708 .

Krmar, Jovana, Stojković, Jovana, Džigal, Merima, Protić, Ana, Maljurić, Nevena, Zečević, Mira, Otašević, Biljana, "Modeling the impact of experimental parameters and molecular structures on APCI signalsʼ intensities of selected antipsychotics using gradient boosted trees" in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy. (2019),
https://hdl.handle.net/21.15107/rcub_farfar_4708 .

TY  - CONF
AU  - Maljurić, Nevena
AU  - Otašević, Biljana
AU  - Krmar, Jovana
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4702
PB  - MSBM
C3  - XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
T1  - Insight in Retention Mechanisms of Basic Analytes in β-Cyclodextrin Modified HPLC
SP  - 37
EP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4702
ER  - 

@conference{
author = "Maljurić, Nevena and Otašević, Biljana and Krmar, Jovana and Zečević, Mira and Protić, Ana",
year = "2019",
publisher = "MSBM",
journal = "XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.",
title = "Insight in Retention Mechanisms of Basic Analytes in β-Cyclodextrin Modified HPLC",
pages = "37-38",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4702"
}

Maljurić, N., Otašević, B., Krmar, J., Zečević, M.,& Protić, A.. (2019). Insight in Retention Mechanisms of Basic Analytes in β-Cyclodextrin Modified HPLC. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
MSBM., 37-38.
https://hdl.handle.net/21.15107/rcub_farfar_4702

Maljurić N, Otašević B, Krmar J, Zečević M, Protić A. Insight in Retention Mechanisms of Basic Analytes in β-Cyclodextrin Modified HPLC. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.. 2019;:37-38.
https://hdl.handle.net/21.15107/rcub_farfar_4702 .

Maljurić, Nevena, Otašević, Biljana, Krmar, Jovana, Zečević, Mira, Protić, Ana, "Insight in Retention Mechanisms of Basic Analytes in β-Cyclodextrin Modified HPLC" in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia. (2019):37-38,
https://hdl.handle.net/21.15107/rcub_farfar_4702 .