TY  - JOUR
AU  - Kovačević, Milena
AU  - Ivanović, Nevena
AU  - Protić, Ana
AU  - Milenković, Danijela
AU  - Mandinić, Zoran
AU  - Puzović, Dragana
AU  - Bajčetić, Miloš
AU  - Popadić, Dušan
AU  - Parojčić, Jelena
AU  - Malenović, Anđelija
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5596
AB  - Digital transformation in education and relevant calls for action are recognised global priorities aimed to support education and training in the digital age. The experiences from the emergency remote teaching during the COVID-19 pandemic and recent research findings reveal relevant advantages, challenges, as well as different students and teaching staff perspectives which should be carefully considered and integrated into institutional strategies and policies to improve and enrich students’ learning experience. The present study aimed to explore health sciences students' perspectives on online teaching and learning (T&L) in four domains—Satisfaction, Motivation, Interaction and Challenges, and to identify the preferred T&L models or tools. A total of 1,041 responses were collected, including 476 dental medicine (45.7%), 399 pharmacy (38.3%), and 166 medical students (15.9%). Overall Satisfaction was quite high (4.0 ± 1.2; out of 5), followed by satisfactory Interaction (3.4 ± 1.4), whereas Motivation was quite low on average (3.0 ± 1.5). Challenges in online T&L were not markedly expressed (3.0 ± 1.6). The majority of students (46.6%) opted for the blended model as the preferred T&L model. Moodle lessons were perceived as the most useful online T&L tool (45.5% of students), followed by video materials (32.2%). Other T&L tools which require more active student's role, such as short test/quiz, and group or team assignment were declared as less favourable. The findings from the current study may contribute to raising the awareness of academic staff and higher institutions management about the student attitudes and needs related to online T&L and inform institutional planning, decision-making and policy development.
PB  - John Wiley & Sons Ltd
T2  - European Journal of Education
T1  - Health sciences students' perspectives on online teaching and learning: Extending the implications beyond the COVID-19 pandemic
DO  - 10.1111/ejed.12660
ER  - 

@article{
author = "Kovačević, Milena and Ivanović, Nevena and Protić, Ana and Milenković, Danijela and Mandinić, Zoran and Puzović, Dragana and Bajčetić, Miloš and Popadić, Dušan and Parojčić, Jelena and Malenović, Anđelija",
year = "2024",
abstract = "Digital transformation in education and relevant calls for action are recognised global priorities aimed to support education and training in the digital age. The experiences from the emergency remote teaching during the COVID-19 pandemic and recent research findings reveal relevant advantages, challenges, as well as different students and teaching staff perspectives which should be carefully considered and integrated into institutional strategies and policies to improve and enrich students’ learning experience. The present study aimed to explore health sciences students' perspectives on online teaching and learning (T&L) in four domains—Satisfaction, Motivation, Interaction and Challenges, and to identify the preferred T&L models or tools. A total of 1,041 responses were collected, including 476 dental medicine (45.7%), 399 pharmacy (38.3%), and 166 medical students (15.9%). Overall Satisfaction was quite high (4.0 ± 1.2; out of 5), followed by satisfactory Interaction (3.4 ± 1.4), whereas Motivation was quite low on average (3.0 ± 1.5). Challenges in online T&L were not markedly expressed (3.0 ± 1.6). The majority of students (46.6%) opted for the blended model as the preferred T&L model. Moodle lessons were perceived as the most useful online T&L tool (45.5% of students), followed by video materials (32.2%). Other T&L tools which require more active student's role, such as short test/quiz, and group or team assignment were declared as less favourable. The findings from the current study may contribute to raising the awareness of academic staff and higher institutions management about the student attitudes and needs related to online T&L and inform institutional planning, decision-making and policy development.",
publisher = "John Wiley & Sons Ltd",
journal = "European Journal of Education",
title = "Health sciences students' perspectives on online teaching and learning: Extending the implications beyond the COVID-19 pandemic",
doi = "10.1111/ejed.12660"
}

Kovačević, M., Ivanović, N., Protić, A., Milenković, D., Mandinić, Z., Puzović, D., Bajčetić, M., Popadić, D., Parojčić, J.,& Malenović, A.. (2024). Health sciences students' perspectives on online teaching and learning: Extending the implications beyond the COVID-19 pandemic. in European Journal of Education
John Wiley & Sons Ltd..
https://doi.org/10.1111/ejed.12660

Kovačević M, Ivanović N, Protić A, Milenković D, Mandinić Z, Puzović D, Bajčetić M, Popadić D, Parojčić J, Malenović A. Health sciences students' perspectives on online teaching and learning: Extending the implications beyond the COVID-19 pandemic. in European Journal of Education. 2024;.
doi:10.1111/ejed.12660 .

Kovačević, Milena, Ivanović, Nevena, Protić, Ana, Milenković, Danijela, Mandinić, Zoran, Puzović, Dragana, Bajčetić, Miloš, Popadić, Dušan, Parojčić, Jelena, Malenović, Anđelija, "Health sciences students' perspectives on online teaching and learning: Extending the implications beyond the COVID-19 pandemic" in European Journal of Education (2024),
https://doi.org/10.1111/ejed.12660 . .

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  - Stojanović, Jevrem
AU  - Krmar, Jovana
AU  - Otašević, Biljana
AU  - Protić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4976
AB  - High-pressure liquid chromatography (HPLC) is a technique of paramount importance in
the analysis of pharmaceuticals because of its ability to separate moderately polar to less polar
compounds, such as drugs and related substances. The concept of green analytical chemistry
(GAC) aims to provide more environmentally friendly and safer analytical methods in terms of
reagents, energy, and waste. One of the major challenges of GAC is to find an appropriate
approach to evaluate the greenness of analytical methods. An extension of GAC, called white
analytical chemistry (WAC), has been introduced to consider not only environmental friendliness,
but also other aspects that contribute to the sustainability of methods, such as analytical and
economic or practical efficiency. HPLC methods are intrinsically not green, due to the high
consumption of toxic organic solvents and the resulting generation of large amounts of toxic
waste. Fortunately, there are many approaches to overcome the non-green character of HPLC
methods. In this article, various modifications of the HPLC methods that increase its
environmental friendliness are presented, as well as the various tools used to evaluate
environmental friendliness. In addition, the new concept of white analytical chemistry is
presented.
AB  - Tečna hromatografija pod visokim pritiskom (HPLC) je tehnika od ogromne važnosti u analitici lekova zbog svoje mogućnosti da razdvoji umereno do manje polarna jedinjenja, kao što su aktivne farmaceutske i srodne supstance. Koncept zelene analitičke hemije (GAC) ima za cilj da obezbedi ekološki prihvatljivije i bezbednije metode u pogledu reagenasa, energije i otpada. Jedan od glavnih izazova GAC je da pronađe odgovarajući pristup za procenu "zelenosti" analitičkih metoda. Proširenje GAC, nazvano bela analitička hemija (WAC), uvedeno je kako bi se uzela u obzir ne samo ekološka prihvatljivost, već i drugi aspekti koji doprinose održivosti metoda, kao što su analitička i ekonomska ili praktična efikasnost. HPLC metode suštinski nisu "zelene" zbog obimne potrošnje toksičnih organskih rastvarača i posledičnog stvaranja velikih količina toksičnog otpada. Srećom, postoji mnogo pristupa za prevazilaženje ne-zelene prirode HPLC metoda. U ovom radu su predstavljene različite modifikacije HPLC metode koje povećavaju ekološku prihvatljivost, kao i različiti alati koji se koriste za procenu ekološke prihvatljivosti. Pored toga, predstavljen je novi koncept bele analitičke hemije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Resource management in HPLC: Unveiling a green face of pharmaceutical analysis
T1  - Upravljanje resursima u HPLC: Otkrivanje zelenog lica farmaceutske analize
VL  - 73
IS  - 2
SP  - 146
EP  - 171
DO  - 10.5937/arhfarm73-43479
ER  - 

@article{
author = "Stojanović, Jevrem and Krmar, Jovana and Otašević, Biljana and Protić, Ana",
year = "2023",
abstract = "High-pressure liquid chromatography (HPLC) is a technique of paramount importance in
the analysis of pharmaceuticals because of its ability to separate moderately polar to less polar
compounds, such as drugs and related substances. The concept of green analytical chemistry
(GAC) aims to provide more environmentally friendly and safer analytical methods in terms of
reagents, energy, and waste. One of the major challenges of GAC is to find an appropriate
approach to evaluate the greenness of analytical methods. An extension of GAC, called white
analytical chemistry (WAC), has been introduced to consider not only environmental friendliness,
but also other aspects that contribute to the sustainability of methods, such as analytical and
economic or practical efficiency. HPLC methods are intrinsically not green, due to the high
consumption of toxic organic solvents and the resulting generation of large amounts of toxic
waste. Fortunately, there are many approaches to overcome the non-green character of HPLC
methods. In this article, various modifications of the HPLC methods that increase its
environmental friendliness are presented, as well as the various tools used to evaluate
environmental friendliness. In addition, the new concept of white analytical chemistry is
presented., Tečna hromatografija pod visokim pritiskom (HPLC) je tehnika od ogromne važnosti u analitici lekova zbog svoje mogućnosti da razdvoji umereno do manje polarna jedinjenja, kao što su aktivne farmaceutske i srodne supstance. Koncept zelene analitičke hemije (GAC) ima za cilj da obezbedi ekološki prihvatljivije i bezbednije metode u pogledu reagenasa, energije i otpada. Jedan od glavnih izazova GAC je da pronađe odgovarajući pristup za procenu "zelenosti" analitičkih metoda. Proširenje GAC, nazvano bela analitička hemija (WAC), uvedeno je kako bi se uzela u obzir ne samo ekološka prihvatljivost, već i drugi aspekti koji doprinose održivosti metoda, kao što su analitička i ekonomska ili praktična efikasnost. HPLC metode suštinski nisu "zelene" zbog obimne potrošnje toksičnih organskih rastvarača i posledičnog stvaranja velikih količina toksičnog otpada. Srećom, postoji mnogo pristupa za prevazilaženje ne-zelene prirode HPLC metoda. U ovom radu su predstavljene različite modifikacije HPLC metode koje povećavaju ekološku prihvatljivost, kao i različiti alati koji se koriste za procenu ekološke prihvatljivosti. Pored toga, predstavljen je novi koncept bele analitičke hemije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Resource management in HPLC: Unveiling a green face of pharmaceutical analysis, Upravljanje resursima u HPLC: Otkrivanje zelenog lica farmaceutske analize",
volume = "73",
number = "2",
pages = "146-171",
doi = "10.5937/arhfarm73-43479"
}

Stojanović, J., Krmar, J., Otašević, B.,& Protić, A.. (2023). Resource management in HPLC: Unveiling a green face of pharmaceutical analysis. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(2), 146-171.
https://doi.org/10.5937/arhfarm73-43479

Stojanović J, Krmar J, Otašević B, Protić A. Resource management in HPLC: Unveiling a green face of pharmaceutical analysis. in Arhiv za farmaciju. 2023;73(2):146-171.
doi:10.5937/arhfarm73-43479 .

Stojanović, Jevrem, Krmar, Jovana, Otašević, Biljana, Protić, Ana, "Resource management in HPLC: Unveiling a green face of pharmaceutical analysis" in Arhiv za farmaciju, 73, no. 2 (2023):146-171,
https://doi.org/10.5937/arhfarm73-43479 . .

TY  - CHAP
AU  - Krmar, Jovana
AU  - Svrkota, Bojana
AU  - Đajić, Nevena
AU  - Stojanović, Jevrem
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4907
AB  - One-factor-at-a-time experimentation was used for a long time as gold-standard
optimization for liquid chromatographic (LC) method development. This approach
has two downsides as it requires a needlessly great number of experimental runs and it
is unable to identify possible factor interactions. At the end of the last century,
however, this problem could be solved with the introduction of new chemometric
strategies. This chapter aims at presenting quantitative structure–retention relationship
(QSRR) models with structuring possibilities, from the point of feature selection
through various machine learning algorithms that can be used in model building, for
internal and external validation of the proposed models. The presented strategies of
QSRR model can be a good starting point for analysts to use and adopt them as a good
practice for their applications. QSRR models can be used in predicting the retention
behavior of compounds, to point out the molecular features governing the retention,
and consequently to gain insight into the retention mechanisms. In terms of these
applications, special attention was drawn to modified chromatographic systems,
characterized by mobile or stationary phase modifications. Although chromatographic
methods are applied in a wide variety of fields, the greatest attention has been devoted
to the analysis of pharmaceuticals.
PB  - IntechOpen
T2  - Novel Aspects of Gas Chromatography and Chemometrics
T1  - QSRR Approach: Application to Retention Mechanism in Liquid Chromatography
SP  - 113
EP  - 141
DO  - 10.5772/intechopen.106245
ER  - 

@inbook{
author = "Krmar, Jovana and Svrkota, Bojana and Đajić, Nevena and Stojanović, Jevrem and Protić, Ana and Otašević, Biljana",
year = "2023",
abstract = "One-factor-at-a-time experimentation was used for a long time as gold-standard
optimization for liquid chromatographic (LC) method development. This approach
has two downsides as it requires a needlessly great number of experimental runs and it
is unable to identify possible factor interactions. At the end of the last century,
however, this problem could be solved with the introduction of new chemometric
strategies. This chapter aims at presenting quantitative structure–retention relationship
(QSRR) models with structuring possibilities, from the point of feature selection
through various machine learning algorithms that can be used in model building, for
internal and external validation of the proposed models. The presented strategies of
QSRR model can be a good starting point for analysts to use and adopt them as a good
practice for their applications. QSRR models can be used in predicting the retention
behavior of compounds, to point out the molecular features governing the retention,
and consequently to gain insight into the retention mechanisms. In terms of these
applications, special attention was drawn to modified chromatographic systems,
characterized by mobile or stationary phase modifications. Although chromatographic
methods are applied in a wide variety of fields, the greatest attention has been devoted
to the analysis of pharmaceuticals.",
publisher = "IntechOpen",
journal = "Novel Aspects of Gas Chromatography and Chemometrics",
booktitle = "QSRR Approach: Application to Retention Mechanism in Liquid Chromatography",
pages = "113-141",
doi = "10.5772/intechopen.106245"
}

Krmar, J., Svrkota, B., Đajić, N., Stojanović, J., Protić, A.,& Otašević, B.. (2023). QSRR Approach: Application to Retention Mechanism in Liquid Chromatography. in Novel Aspects of Gas Chromatography and Chemometrics
IntechOpen., 113-141.
https://doi.org/10.5772/intechopen.106245

Krmar J, Svrkota B, Đajić N, Stojanović J, Protić A, Otašević B. QSRR Approach: Application to Retention Mechanism in Liquid Chromatography. in Novel Aspects of Gas Chromatography and Chemometrics. 2023;:113-141.
doi:10.5772/intechopen.106245 .

Krmar, Jovana, Svrkota, Bojana, Đajić, Nevena, Stojanović, Jevrem, Protić, Ana, Otašević, Biljana, "QSRR Approach: Application to Retention Mechanism in Liquid Chromatography" in Novel Aspects of Gas Chromatography and Chemometrics (2023):113-141,
https://doi.org/10.5772/intechopen.106245 . .

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  - Krmar, Jovana
AU  - Tolić Stojadinović, Ljiljana
AU  - Đurkić, Tatjana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4881
AB  - A priori estimation of analyte response is crucial for the efficient development of liquid chromatography–electrospray ionization/mass spectrometry (LC–ESI/MS) methods, but remains a demanding task given the lack of knowledge about the factors affecting the experimental outcome. In this research, we address the challenge of discovering the interactive relationship between signal response and structural properties, method parameters and solvent-related descriptors throughout an approach featuring quantitative structure–property relationship (QSPR) and design of experiments (DoE). To systematically investigate the experimental domain within which QSPR prediction should be undertaken, we varied LC and instrumental factors according to the Box-Behnken DoE scheme. Seven compounds, including aripiprazole and its impurities, were subjected to 57 different experimental conditions, resulting in 399 LC–ESI/MS data endpoints. To obtain a more standard distribution of the measured response, the peak areas were log-transformed before modeling. QSPR predictions were made using features selected by Genetic Algorithm (GA) and providing Gradient Boosted Trees (GBT) with training data. Proposed model showed satisfactory performance on test data with a RMSEP of 1.57 % and a of 96.48 %. This is the first QSPR study in LC–ESI/MS that provided a holistic overview of the analyte’s response behavior across the experimental and chemical space. Since intramolecular electronic effects and molecular size were given great importance, the GA–GBT model improved the understanding of signal response generation of model compounds. It also highlighted the need to fine-tune the parameters affecting desolvation and droplet charging efficiency.
PB  - Elsevier Inc.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities
VL  - 233
DO  - 10.1016/j.jpba.2023.115422
ER  - 

@article{
author = "Krmar, Jovana and Tolić Stojadinović, Ljiljana and Đurkić, Tatjana and Protić, Ana and Otašević, Biljana",
year = "2023",
abstract = "A priori estimation of analyte response is crucial for the efficient development of liquid chromatography–electrospray ionization/mass spectrometry (LC–ESI/MS) methods, but remains a demanding task given the lack of knowledge about the factors affecting the experimental outcome. In this research, we address the challenge of discovering the interactive relationship between signal response and structural properties, method parameters and solvent-related descriptors throughout an approach featuring quantitative structure–property relationship (QSPR) and design of experiments (DoE). To systematically investigate the experimental domain within which QSPR prediction should be undertaken, we varied LC and instrumental factors according to the Box-Behnken DoE scheme. Seven compounds, including aripiprazole and its impurities, were subjected to 57 different experimental conditions, resulting in 399 LC–ESI/MS data endpoints. To obtain a more standard distribution of the measured response, the peak areas were log-transformed before modeling. QSPR predictions were made using features selected by Genetic Algorithm (GA) and providing Gradient Boosted Trees (GBT) with training data. Proposed model showed satisfactory performance on test data with a RMSEP of 1.57 % and a of 96.48 %. This is the first QSPR study in LC–ESI/MS that provided a holistic overview of the analyte’s response behavior across the experimental and chemical space. Since intramolecular electronic effects and molecular size were given great importance, the GA–GBT model improved the understanding of signal response generation of model compounds. It also highlighted the need to fine-tune the parameters affecting desolvation and droplet charging efficiency.",
publisher = "Elsevier Inc.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities",
volume = "233",
doi = "10.1016/j.jpba.2023.115422"
}

Krmar, J., Tolić Stojadinović, L., Đurkić, T., Protić, A.,& Otašević, B.. (2023). Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Inc.., 233.
https://doi.org/10.1016/j.jpba.2023.115422

Krmar J, Tolić Stojadinović L, Đurkić T, Protić A, Otašević B. Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities. in Journal of Pharmaceutical and Biomedical Analysis. 2023;233.
doi:10.1016/j.jpba.2023.115422 .

Krmar, Jovana, Tolić Stojadinović, Ljiljana, Đurkić, Tatjana, Protić, Ana, Otašević, Biljana, "Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities" in Journal of Pharmaceutical and Biomedical Analysis, 233 (2023),
https://doi.org/10.1016/j.jpba.2023.115422 . .

TY  - JOUR
AU  - Walther, Rasmus
AU  - Krmar, Jovana
AU  - Leistner, Adrian
AU  - Svrkota, Bojana
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Holzgrabe, Ulrike
AU  - Protić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4698
AB  - An alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs) is urgently needed. The objective was therefore to propose a robust liquid chromatography method with charged aerosol detection for the analysis of polysorbate 80 (PS80) and magnesium stearate. FAs with different numbers of carbon atoms in the chain necessitated the use of a gradient method with a Hypersil Gold C18 column and acetonitrile as organic modifier. The risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR). Formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate were identified as critical method parameters (CMPs). The initial and final percentages of acetonitrile were fixed while the remaining CMPs were fine-tuned using response surface methodology. Critical method attributes included the baseline separation of adjacent peaks (α-linolenic and myristic acid, and oleic and petroselinic acid) and the retention factor of the last compound eluted, stearic acid. The MODR was calculated by Monte Carlo simulations with a probability equal or greater than 90%. Finally, the column temperature was set at 33 °C, the flow rate was 0.575 mL/min, and acetonitrile linearly increased from 70 to 80% (v/v) within 14.2 min.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids
VL  - 16
IS  - 4
DO  - 10.3390/ph16040478
ER  - 

@article{
author = "Walther, Rasmus and Krmar, Jovana and Leistner, Adrian and Svrkota, Bojana and Otašević, Biljana and Malenović, Anđelija and Holzgrabe, Ulrike and Protić, Ana",
year = "2023",
abstract = "An alternative to the time-consuming and error-prone pharmacopoeial gas chromatography method for the analysis of fatty acids (FAs) is urgently needed. The objective was therefore to propose a robust liquid chromatography method with charged aerosol detection for the analysis of polysorbate 80 (PS80) and magnesium stearate. FAs with different numbers of carbon atoms in the chain necessitated the use of a gradient method with a Hypersil Gold C18 column and acetonitrile as organic modifier. The risk-based Analytical Quality by Design approach was applied to define the Method Operable Design Region (MODR). Formic acid concentration, initial and final percentages of acetonitrile, gradient elution time, column temperature, and mobile phase flow rate were identified as critical method parameters (CMPs). The initial and final percentages of acetonitrile were fixed while the remaining CMPs were fine-tuned using response surface methodology. Critical method attributes included the baseline separation of adjacent peaks (α-linolenic and myristic acid, and oleic and petroselinic acid) and the retention factor of the last compound eluted, stearic acid. The MODR was calculated by Monte Carlo simulations with a probability equal or greater than 90%. Finally, the column temperature was set at 33 °C, the flow rate was 0.575 mL/min, and acetonitrile linearly increased from 70 to 80% (v/v) within 14.2 min.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids",
volume = "16",
number = "4",
doi = "10.3390/ph16040478"
}

Walther, R., Krmar, J., Leistner, A., Svrkota, B., Otašević, B., Malenović, A., Holzgrabe, U.,& Protić, A.. (2023). Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids. in Pharmaceuticals
MDPI., 16(4).
https://doi.org/10.3390/ph16040478

Walther R, Krmar J, Leistner A, Svrkota B, Otašević B, Malenović A, Holzgrabe U, Protić A. Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids. in Pharmaceuticals. 2023;16(4).
doi:10.3390/ph16040478 .

Walther, Rasmus, Krmar, Jovana, Leistner, Adrian, Svrkota, Bojana, Otašević, Biljana, Malenović, Anđelija, Holzgrabe, Ulrike, Protić, Ana, "Analytical Quality by Design: Achieving Robustness of an LC-CAD Method for the Analysis of Non-Volatile Fatty Acids" in Pharmaceuticals, 16, no. 4 (2023),
https://doi.org/10.3390/ph16040478 . .

TY  - JOUR
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4414
AB  - Resolving complex sample mixtures by liquid chromatography in a single run is challenging. The so-called mixed-mode liquid chromatography (MMLC) which combines several retention mechanisms within a single column, can provide resource-efficient separation of solutes of diverse nature. The Acclaim Mixed-Mode WCX-1 column, encompassing hydrophobic and weak cation exchange interactions, was employed for the analysis of small drug molecules. The stationary phase's interaction abilities were assessed by analysing molecules of different ionisation potentials. Mixed Quantitative Structure-Retention Relationship (QSRR) models were developed for revealing significant experimental parameters (EPs) and molecular features governing molecular retention. According to the plan of Face-Centred Central Composite Design, EPs (column temperature, acetonitrile content, pH and buffer concentration of aqueous mobile phase) variations were included in QSRR modelling. QSRRs were developed upon the whole data set (global model) and upon discrete parts, related to similarly ionized analytes (local models) by applying gradient boosted trees as a regression tool. Root mean squared errors of prediction for global and local QSRR models for cations, anions and neutrals were respectively 0.131; 0.105; 0.102 and 0.042 with the coefficient of determination 0.947; 0.872; 0.954 and 0.996, indicating satisfactory performances of all models, with slightly better accuracy of local ones. The research showed that influences of EPs were dependant on the molecule's ionisation potential. The molecular descriptors highlighted by models pointed out that electrostatic and hydrophobic interactions and hydrogen bonds participate in the retention process. The molecule's conformation significance was evaluated along with the topological relationship between the interaction centres, explicitly determined for each molecular species through local models. All models showed good molecular retention predictability thus showing potential for facilitating the method development.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - The secret of reversed-phase/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis
VL  - 1690
DO  - 10.1016/j.chroma.2023.463776
ER  - 

@article{
author = "Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Otašević, Biljana",
year = "2023",
abstract = "Resolving complex sample mixtures by liquid chromatography in a single run is challenging. The so-called mixed-mode liquid chromatography (MMLC) which combines several retention mechanisms within a single column, can provide resource-efficient separation of solutes of diverse nature. The Acclaim Mixed-Mode WCX-1 column, encompassing hydrophobic and weak cation exchange interactions, was employed for the analysis of small drug molecules. The stationary phase's interaction abilities were assessed by analysing molecules of different ionisation potentials. Mixed Quantitative Structure-Retention Relationship (QSRR) models were developed for revealing significant experimental parameters (EPs) and molecular features governing molecular retention. According to the plan of Face-Centred Central Composite Design, EPs (column temperature, acetonitrile content, pH and buffer concentration of aqueous mobile phase) variations were included in QSRR modelling. QSRRs were developed upon the whole data set (global model) and upon discrete parts, related to similarly ionized analytes (local models) by applying gradient boosted trees as a regression tool. Root mean squared errors of prediction for global and local QSRR models for cations, anions and neutrals were respectively 0.131; 0.105; 0.102 and 0.042 with the coefficient of determination 0.947; 0.872; 0.954 and 0.996, indicating satisfactory performances of all models, with slightly better accuracy of local ones. The research showed that influences of EPs were dependant on the molecule's ionisation potential. The molecular descriptors highlighted by models pointed out that electrostatic and hydrophobic interactions and hydrogen bonds participate in the retention process. The molecule's conformation significance was evaluated along with the topological relationship between the interaction centres, explicitly determined for each molecular species through local models. All models showed good molecular retention predictability thus showing potential for facilitating the method development.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "The secret of reversed-phase/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis",
volume = "1690",
doi = "10.1016/j.chroma.2023.463776"
}

Svrkota, B., Krmar, J., Protić, A.,& Otašević, B.. (2023). The secret of reversed-phase/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis. in Journal of Chromatography A
Elsevier B.V.., 1690.
https://doi.org/10.1016/j.chroma.2023.463776

Svrkota B, Krmar J, Protić A, Otašević B. The secret of reversed-phase/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis. in Journal of Chromatography A. 2023;1690.
doi:10.1016/j.chroma.2023.463776 .

Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Otašević, Biljana, "The secret of reversed-phase/weak cation exchange retention mechanisms in mixed-mode liquid chromatography applied for small drug molecule analysis" in Journal of Chromatography A, 1690 (2023),
https://doi.org/10.1016/j.chroma.2023.463776 . .

TY  - CHAP
AU  - Đajić, Nevena
AU  - Protić, Ana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4906
PB  - Marcel Dekker Inc.
T2  - Advances in Chromatography
T1  - Advanced QSRR Modeling in β-CD-Modifed RP-HPLC System
VL  - 59
SP  - 99
EP  - 144
DO  - 10.1201/9781003330080-3
ER  - 

@inbook{
author = "Đajić, Nevena and Protić, Ana",
year = "2023",
publisher = "Marcel Dekker Inc.",
journal = "Advances in Chromatography",
booktitle = "Advanced QSRR Modeling in β-CD-Modifed RP-HPLC System",
volume = "59",
pages = "99-144",
doi = "10.1201/9781003330080-3"
}

Đajić, N.,& Protić, A.. (2023). Advanced QSRR Modeling in β-CD-Modifed RP-HPLC System. in Advances in Chromatography
Marcel Dekker Inc.., 59, 99-144.
https://doi.org/10.1201/9781003330080-3

Đajić N, Protić A. Advanced QSRR Modeling in β-CD-Modifed RP-HPLC System. in Advances in Chromatography. 2023;59:99-144.
doi:10.1201/9781003330080-3 .

Đajić, Nevena, Protić, Ana, "Advanced QSRR Modeling in β-CD-Modifed RP-HPLC System" in Advances in Chromatography, 59 (2023):99-144,
https://doi.org/10.1201/9781003330080-3 . .

TY  - JOUR
AU  - Tomić, Jovana
AU  - Đajić, Nevena
AU  - Agbaba, Danica
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4331
AB  - This paper is aimed at developing a gradient elution reversed-phase high-performance liquid chromatography (RP-HPLC) method for the separation of a complex mixture composed of ivabradine and its eleven impurities, in a reasonable timeframe. In order to obtain a robust and reliable HPLC method for separation of this mixture, Analytical Quality by Design (AQbD) was applied. This approach demonstrated to be useful in development of a long lasting life cycle methods. Four chromatographic variables were defined as key method parameters (KMPs) and optimized towards the analytical target profile (ATP). Designated KMPs were initial and final amount of acetonitrile in the mobile phase, pH value of the aqueous phase and gradient time, while resolutions of critical peak pairs were denoted as critical method attributes (CMAs). Relationships between KMPs and CMAs were obtained with the aid of Design of Experiments (DoEs) methodology among which Box-Behnken design (BBD) was employed to gain valid mathematical models. Obtained mathematical equations were used to construct the Design Space (DS) and select reliable optimal separation conditions. They included 11% (v/v) and 34% (v/v) of initial and final amount of acetonitrile, respectively, as well as 45 min of gradient elution time and 20 mM ammonium acetate as aqueous mobile phase with pH set to 7.35. The possibility to separate the diastereoisomers of impurity X was also evaluated. It was demonstrated that this separation could not be achieved in gradient elution mode within the defined variable domains and in a reasonable time span. The developed method was validated according to ICH Q2 (R1) guideline and met all the required criteria.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach
VL  - 34
IS  - 1
SP  - 1
EP  - 11
DO  - 10.1556/1326.2021.00885
ER  - 

@article{
author = "Tomić, Jovana and Đajić, Nevena and Agbaba, Danica and Otašević, Biljana and Malenović, Anđelija and Protić, Ana",
year = "2022",
abstract = "This paper is aimed at developing a gradient elution reversed-phase high-performance liquid chromatography (RP-HPLC) method for the separation of a complex mixture composed of ivabradine and its eleven impurities, in a reasonable timeframe. In order to obtain a robust and reliable HPLC method for separation of this mixture, Analytical Quality by Design (AQbD) was applied. This approach demonstrated to be useful in development of a long lasting life cycle methods. Four chromatographic variables were defined as key method parameters (KMPs) and optimized towards the analytical target profile (ATP). Designated KMPs were initial and final amount of acetonitrile in the mobile phase, pH value of the aqueous phase and gradient time, while resolutions of critical peak pairs were denoted as critical method attributes (CMAs). Relationships between KMPs and CMAs were obtained with the aid of Design of Experiments (DoEs) methodology among which Box-Behnken design (BBD) was employed to gain valid mathematical models. Obtained mathematical equations were used to construct the Design Space (DS) and select reliable optimal separation conditions. They included 11% (v/v) and 34% (v/v) of initial and final amount of acetonitrile, respectively, as well as 45 min of gradient elution time and 20 mM ammonium acetate as aqueous mobile phase with pH set to 7.35. The possibility to separate the diastereoisomers of impurity X was also evaluated. It was demonstrated that this separation could not be achieved in gradient elution mode within the defined variable domains and in a reasonable time span. The developed method was validated according to ICH Q2 (R1) guideline and met all the required criteria.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach",
volume = "34",
number = "1",
pages = "1-11",
doi = "10.1556/1326.2021.00885"
}

Tomić, J., Đajić, N., Agbaba, D., Otašević, B., Malenović, A.,& Protić, A.. (2022). Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(1), 1-11.
https://doi.org/10.1556/1326.2021.00885

Tomić J, Đajić N, Agbaba D, Otašević B, Malenović A, Protić A. Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach. in Acta Chromatographica. 2022;34(1):1-11.
doi:10.1556/1326.2021.00885 .

Tomić, Jovana, Đajić, Nevena, Agbaba, Danica, Otašević, Biljana, Malenović, Anđelija, Protić, Ana, "Robust optimization of gradient RP HPLC method for simultaneous determination of ivabradine and its eleven related substances by AQbD approach" in Acta Chromatographica, 34, no. 1 (2022):1-11,
https://doi.org/10.1556/1326.2021.00885 . .

TY  - JOUR
AU  - Krmar, Jovana
AU  - Džigal, Merima
AU  - Stojković, Jovana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4081
AB  - Predicting the response signal in Atmospheric Pressure Chemical Ionization - Mass Spectrometry (APCI-MS) systems appears to be considerably challenging due to a gap in knowledge of governing factors and nature of their relationship with response. In this regard, signal intensity is optimized for each analyte separately through trialand- error approach which impairs the method development and depletes numerous resources. To tackle the given issue, here we proposed the Quantitative Structure - Property Relationship (QSPR) model that estimated the ion signal based on molecular descriptors of tested compounds. In particular, the QSPR model was developed using APCI-MS data acquired for 8 chemical compounds under 41 different experimental conditions. Antipsychotics, namely, sulpiride, risperidone, aripiprazole, bifeprunox, ziprasidone and its three impurities, were selected as model substances to undergo APCI ionization. Experimental (instrumental and solventrelated) parameters were varied according to the scheme of Box-Behnken Design. Gradient Boosted Trees (GBT) technique was used to model sophisticated inputs – output relationships of the monitored system. The GBT algorithm with optimized hyper-parameters (16 estimators, learning rate set to 0.55 and maximal depth set to 7) built a so-called mixed model that yielded satisfactory predictive performance (Root Mean Square Error of Prediction: 5.98%; coefficient of determination: 97.1%). According to the built-in feature selection method, GBT identified experimental factors impacting nebulization and vaporization efficiency, i.e. descriptors related to hydrophobicity and molecular polarizability as the major determinants of observed APCI behavior. Therefore, the proposed model has shed light on the parameters and factors’ interactions that govern the generation of APCI ion signals for the analytes with diverse physical-chemical properties. The established QSPR patterns could be reliably used to predict APCI-MS signal in a variety of experimental environ
PB  - Elsevier B.V.
T2  - Chemometrics and Intelligent Laboratory Systems
T1  - Gradient Boosted Tree model: A fast track tool for predicting the Atmospheric Pressure Chemical Ionization-Mass Spectrometry signal of antipsychotics based on molecular features and experimental settings
VL  - 224
DO  - 10.1016/j.chemolab.2022.104554
ER  - 

@article{
author = "Krmar, Jovana and Džigal, Merima and Stojković, Jovana and Protić, Ana and Otašević, Biljana",
year = "2022",
abstract = "Predicting the response signal in Atmospheric Pressure Chemical Ionization - Mass Spectrometry (APCI-MS) systems appears to be considerably challenging due to a gap in knowledge of governing factors and nature of their relationship with response. In this regard, signal intensity is optimized for each analyte separately through trialand- error approach which impairs the method development and depletes numerous resources. To tackle the given issue, here we proposed the Quantitative Structure - Property Relationship (QSPR) model that estimated the ion signal based on molecular descriptors of tested compounds. In particular, the QSPR model was developed using APCI-MS data acquired for 8 chemical compounds under 41 different experimental conditions. Antipsychotics, namely, sulpiride, risperidone, aripiprazole, bifeprunox, ziprasidone and its three impurities, were selected as model substances to undergo APCI ionization. Experimental (instrumental and solventrelated) parameters were varied according to the scheme of Box-Behnken Design. Gradient Boosted Trees (GBT) technique was used to model sophisticated inputs – output relationships of the monitored system. The GBT algorithm with optimized hyper-parameters (16 estimators, learning rate set to 0.55 and maximal depth set to 7) built a so-called mixed model that yielded satisfactory predictive performance (Root Mean Square Error of Prediction: 5.98%; coefficient of determination: 97.1%). According to the built-in feature selection method, GBT identified experimental factors impacting nebulization and vaporization efficiency, i.e. descriptors related to hydrophobicity and molecular polarizability as the major determinants of observed APCI behavior. Therefore, the proposed model has shed light on the parameters and factors’ interactions that govern the generation of APCI ion signals for the analytes with diverse physical-chemical properties. The established QSPR patterns could be reliably used to predict APCI-MS signal in a variety of experimental environ",
publisher = "Elsevier B.V.",
journal = "Chemometrics and Intelligent Laboratory Systems",
title = "Gradient Boosted Tree model: A fast track tool for predicting the Atmospheric Pressure Chemical Ionization-Mass Spectrometry signal of antipsychotics based on molecular features and experimental settings",
volume = "224",
doi = "10.1016/j.chemolab.2022.104554"
}

Krmar, J., Džigal, M., Stojković, J., Protić, A.,& Otašević, B.. (2022). Gradient Boosted Tree model: A fast track tool for predicting the Atmospheric Pressure Chemical Ionization-Mass Spectrometry signal of antipsychotics based on molecular features and experimental settings. in Chemometrics and Intelligent Laboratory Systems
Elsevier B.V.., 224.
https://doi.org/10.1016/j.chemolab.2022.104554

Krmar J, Džigal M, Stojković J, Protić A, Otašević B. Gradient Boosted Tree model: A fast track tool for predicting the Atmospheric Pressure Chemical Ionization-Mass Spectrometry signal of antipsychotics based on molecular features and experimental settings. in Chemometrics and Intelligent Laboratory Systems. 2022;224.
doi:10.1016/j.chemolab.2022.104554 .

Krmar, Jovana, Džigal, Merima, Stojković, Jovana, Protić, Ana, Otašević, Biljana, "Gradient Boosted Tree model: A fast track tool for predicting the Atmospheric Pressure Chemical Ionization-Mass Spectrometry signal of antipsychotics based on molecular features and experimental settings" in Chemometrics and Intelligent Laboratory Systems, 224 (2022),
https://doi.org/10.1016/j.chemolab.2022.104554 . .

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

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

Malenović, A., Kovačević, M., Ivanović, N., Protić, A.,& Parojčić, J.. (2022). Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade. in Pharmacy Education
European Association of Faculties of Pharmacy., 22(3), 8-8.
https://doi.org/10.46542/pe.2022.223.135

Malenović A, Kovačević M, Ivanović N, Protić A, Parojčić J. Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade. in Pharmacy Education. 2022;22(3):8-8.
doi:10.46542/pe.2022.223.135 .

Malenović, Anđelija, Kovačević, Milena, Ivanović, Nevena, Protić, Ana, Parojčić, Jelena, "Pharmacy students’ perspective on online lectures during the COVID-19 pandemic: A case study from the University of Belgrade" in Pharmacy Education, 22, no. 3 (2022):8-8,
https://doi.org/10.46542/pe.2022.223.135 . .

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

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

Malenović, A., Kovačević, M., Ivanović, N., Protić, A.,& Parojčić, J.. (2022). Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book
European Association of Faculties of Pharmacy..
https://hdl.handle.net/21.15107/rcub_farfar_4375

Malenović A, Kovačević M, Ivanović N, Protić A, Parojčić J. Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade.. in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4375 .

Malenović, Anđelija, Kovačević, Milena, Ivanović, Nevena, Protić, Ana, Parojčić, Jelena, "Pharmacy students' perspectives on online lectures during the COVID – 19 pandemic – case study from the University of Belgrade." in EAFP Conference 2022, Towards Pharmacy 5.0 Education - Abstract Book (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4375 .

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  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Đajić, Nevena
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4692
AB  - Introduction: Active pharmaceutical ingredients
(APIs) are often used in salt form, which is why the
inclusion of weak cation exchange (WCX), in
addition to reverse-phased (RP) hydrophobic
interactions, could improve APIs’ separation (1).
Due to the limited knowledge about the RP/WCX
bimodal system, the aim was to elucidate the
experimental factors’ influence on the retention of
diverse ionized APIs, and provide efficient method
optimization.
Materials and Methods: Acidic (ibuprofen (IB),
aceclofenac (AC)) and basic (escitalopram (ES),
aripiprazole (AR), atomoxetine (AT)) analytes were
tested. Chromatography experiments were
performed on Thermo Acclaim Mixed Mode WCX-
1 (5 μm, 3x10 mm) column. Mobile phase
consisted of ACN (30-50% (v/v)) and acetic buffer
(pH 3.8 - 5.6; ionic strength (I) 20-40 mM).
Temperature (T) was varied in range 30–38 °C.
Variations of these factors were conducted
according to Full Factorial Design 24. Optimization
phase was executed by using face-centered
Central Composite Design (Design-Expert 7.0.0).
Results: Screening results showed that %ACN
had the greatest impact on analytes’ retention
factors (k), so increasing in %ACN caused a
decrease in k. T had the same effect, but much less
pronounced. Changes in mobile phase pH affected
k, with the opposite effect on anionic and cationic species. This is attributed to greater ionization of
stationary phases’ carboxylic groups at higher pH.
As consequence, repulsive interactions with
anionic and attractive interactions with the cationic
analytes, are enhanced, vice versa (2). Ionic
strength had much more influence on cationic
analytes than on anionic ones. Due to all the
above, all of four factors were included during
optimization phase. Optimization goals were set so
that k values were in range 1–10 (k(AR)<10,
k(AC)>10, k(IB) in range) and selectivity of critical
peak pair α(AT/ES)>1.3. All derived mathematical
models were statistically estimated (R2, adj. R2,
pred. R2>0.95). Set of optimal conditions which is
47% (v/v) ACN, acetic buffer (40 mМ, pH 3.8) and
temperature 30 °C was determined using
Derringer’s desirability function.
Conclusions: Experimental parameters with
significant influence on retention in bimodal
RP/WCX system were evaluated, and upon that
method was successfully optimized.
PB  - Ankara University Faculty of Pharmacy
C3  - 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey
T1  - Chemometrically supported optimization of RP/WCX-HPLC method
SP  - 228
EP  - 229
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4692
ER  - 

@conference{
author = "Svrkota, Bojana and Krmar, Jovana and Đajić, Nevena and Protić, Ana and Otašević, Biljana",
year = "2022",
abstract = "Introduction: Active pharmaceutical ingredients
(APIs) are often used in salt form, which is why the
inclusion of weak cation exchange (WCX), in
addition to reverse-phased (RP) hydrophobic
interactions, could improve APIs’ separation (1).
Due to the limited knowledge about the RP/WCX
bimodal system, the aim was to elucidate the
experimental factors’ influence on the retention of
diverse ionized APIs, and provide efficient method
optimization.
Materials and Methods: Acidic (ibuprofen (IB),
aceclofenac (AC)) and basic (escitalopram (ES),
aripiprazole (AR), atomoxetine (AT)) analytes were
tested. Chromatography experiments were
performed on Thermo Acclaim Mixed Mode WCX-
1 (5 μm, 3x10 mm) column. Mobile phase
consisted of ACN (30-50% (v/v)) and acetic buffer
(pH 3.8 - 5.6; ionic strength (I) 20-40 mM).
Temperature (T) was varied in range 30–38 °C.
Variations of these factors were conducted
according to Full Factorial Design 24. Optimization
phase was executed by using face-centered
Central Composite Design (Design-Expert 7.0.0).
Results: Screening results showed that %ACN
had the greatest impact on analytes’ retention
factors (k), so increasing in %ACN caused a
decrease in k. T had the same effect, but much less
pronounced. Changes in mobile phase pH affected
k, with the opposite effect on anionic and cationic species. This is attributed to greater ionization of
stationary phases’ carboxylic groups at higher pH.
As consequence, repulsive interactions with
anionic and attractive interactions with the cationic
analytes, are enhanced, vice versa (2). Ionic
strength had much more influence on cationic
analytes than on anionic ones. Due to all the
above, all of four factors were included during
optimization phase. Optimization goals were set so
that k values were in range 1–10 (k(AR)<10,
k(AC)>10, k(IB) in range) and selectivity of critical
peak pair α(AT/ES)>1.3. All derived mathematical
models were statistically estimated (R2, adj. R2,
pred. R2>0.95). Set of optimal conditions which is
47% (v/v) ACN, acetic buffer (40 mМ, pH 3.8) and
temperature 30 °C was determined using
Derringer’s desirability function.
Conclusions: Experimental parameters with
significant influence on retention in bimodal
RP/WCX system were evaluated, and upon that
method was successfully optimized.",
publisher = "Ankara University Faculty of Pharmacy",
journal = "13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey",
title = "Chemometrically supported optimization of RP/WCX-HPLC method",
pages = "228-229",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4692"
}

Svrkota, B., Krmar, J., Đajić, N., Protić, A.,& Otašević, B.. (2022). Chemometrically supported optimization of RP/WCX-HPLC method. in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey
Ankara University Faculty of Pharmacy., 228-229.
https://hdl.handle.net/21.15107/rcub_farfar_4692

Svrkota B, Krmar J, Đajić N, Protić A, Otašević B. Chemometrically supported optimization of RP/WCX-HPLC method. in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey. 2022;:228-229.
https://hdl.handle.net/21.15107/rcub_farfar_4692 .

Svrkota, Bojana, Krmar, Jovana, Đajić, Nevena, Protić, Ana, Otašević, Biljana, "Chemometrically supported optimization of RP/WCX-HPLC method" in 13th International Symposium on Pharmaceutical Sciences (ISOPS), June 22-25, 2021, Ankara, Turkey (2022):228-229,
https://hdl.handle.net/21.15107/rcub_farfar_4692 .

TY  - CONF
AU  - Krmar, Jovana
AU  - Tolić-Stojadinović, Ljiljana
AU  - Vukićević, Milan
AU  - Đurkić, Tatjana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4691
PB  - University of Mons (Belgium)
C3  - 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
T1  - The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4691
ER  - 

@conference{
author = "Krmar, Jovana and Tolić-Stojadinović, Ljiljana and Vukićević, Milan and Đurkić, Tatjana and Protić, Ana and Otašević, Biljana",
year = "2022",
publisher = "University of Mons (Belgium)",
journal = "12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book",
title = "The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4691"
}

Krmar, J., Tolić-Stojadinović, L., Vukićević, M., Đurkić, T., Protić, A.,& Otašević, B.. (2022). The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
University of Mons (Belgium)..
https://hdl.handle.net/21.15107/rcub_farfar_4691

Krmar J, Tolić-Stojadinović L, Vukićević M, Đurkić T, Protić A, Otašević B. The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4691 .

Krmar, Jovana, Tolić-Stojadinović, Ljiljana, Vukićević, Milan, Đurkić, Tatjana, Protić, Ana, Otašević, Biljana, "The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?" in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4691 .

TY  - CONF
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4689
PB  - University of Mons (Belgium)
C3  - 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
T1  - Mixed-mode RP/WCX chromatographic system evaluation using QSRR modelling approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4689
ER  - 

@conference{
author = "Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Otašević, Biljana",
year = "2022",
publisher = "University of Mons (Belgium)",
journal = "12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book",
title = "Mixed-mode RP/WCX chromatographic system evaluation using QSRR modelling approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4689"
}

Svrkota, B., Krmar, J., Protić, A.,& Otašević, B.. (2022). Mixed-mode RP/WCX chromatographic system evaluation using QSRR modelling approach. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
University of Mons (Belgium)..
https://hdl.handle.net/21.15107/rcub_farfar_4689

Svrkota B, Krmar J, Protić A, Otašević B. Mixed-mode RP/WCX chromatographic system evaluation using QSRR modelling approach. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4689 .

Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Otašević, Biljana, "Mixed-mode RP/WCX chromatographic system evaluation using QSRR modelling approach" in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4689 .

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  - CONF
AU  - Svrkota, Bojana
AU  - Krmar, Jovana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4524
AB  - Mixed-Mode Liquid Chromatography (MMLC) includes several separation
mechanisms in a single column, which is why MMLC can analyze compounds in a broad
range of polarities and ionization potentials in a single run (1). Acclaim Mixed-Mode WCX-1
column with the ability to expose hydrophobic and weak cation exchange interactions was
thus selected to analyse a challenging mixture of neutral and cationic forms: ergotamine,
mecloxamine, camylofin, caffeine and propyphenazone, used as a fixed combination. MMLC
method was developed in line with Analytical Quality by Design (AQbD) approach implying
the scientifically-based understanding of process properties and risk-based management of
the method life cycle. AQbD refers to pre-definition of the method’s Analytical Target Profile
(ATP) by means of baseline separations within the shortest possible time, as well as
definition of Critical Method Attributes (CMAs) as a measure of method quality and Critical
Method Parameters (CMPs) affecting CMAs (2). Acetonitrile content, pH and acetate buffer
concentration were selected as CMPs since retention mechanism expression in MMLC
strongly depends on the mobile phase characteristics. The dependence of CMAs on CMPs was
revealed following a face-centred central composition design plan of experiments and
accompanying mathematical models, coefficients and standard error values. Design Space in
which ATP is achieved with a high level of reliability (π = 90%), was determined by Monte
Carlo simulations taking error distribution into account. Its margins pointed out to the
working point that assures proper method robustness (pH 5.2, 90 mM acetate buffer solution
and 48% (v/v) of acetonitrile).
AB  - Multimodalna tečna hromatografija (Mixed‐Mode Liquid Chromatography – MMLC)
uključuje nekoliko mehanizama razdvajanja u jednoj koloni, zbog čega se ova tehnika može
koristiti za simultanu analizu jedinjenja širokog opsega polarnosti i jonizacionog potencijala
(1). Acclaim Mixed‐Mode WCX‐1 kolona sa sposobnošću ekspresije hidrofobnih i interakcija
slabe katjonske izmene, je odabrana za analizu izazovne smeše neutralnih i katjonskih oblika
analita: ergotamina, mekloksamina, kamilofina, kofeina i propifenazona, koji se primenjuju u
fiksnoj kombinaciji. MMLC metoda je razvijena u skladu sa pristupom ugradnje kvaliteta kroz
dizajn (Analytical Quality by Design – AQbD) koji podrazumeva naučno zasnovano
razumevanje svojstava procesa i upravljanje životnim ciklusom metode prema riziku. AQbD
se odnosi na unapred definisanje analitičkog ciljanog profila metode (Analytical Target
Profile - ATP) odnosno razdvajanje na baznoj liniji za što kraće vreme, kao i na definisanje
kritičnih osobina metode (Critical Method Attributes - CMA) kao mere kvaliteta metode i
kritičnih parametara metode (Critical Method Parameters - CMP) koji utiču na CMA (2).
Sadržaj acetonitrila, pH i koncentracija acetatnog pufera izabrani su kao CMP, pošto
ekspresija MMLC retencionih mehanizma zavisi od karakteristika mobilne faze. Zavisnost
CMA od CMP definisana je pomoću plana eksperimenata usklađenim sa centralnim
kompozicionim dizajnom, ka centru orijentisanim i pratećim matematičkim modelima,
koeficijentima i vrednostima standardne greške. Prostor dizajna u kome se ATP postiže sa
visokim nivoom pouzdanosti (π = 90%) određen je Monte Karlo simulacijama uzimajuć i u
obzir distribuciju grešaka. Njegov okvir ukazuje na radnu tačku koja obezbeđuje
odgovarajuć u robusnost metode (pH 5,2, 90 mM rastvor acetatnog pufera i 48% (v/v)
acetonitrila).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Robust mixed-mode chromatography method development using Analytical Quality by Design approach for analysis of selected drugs
T1  - Robustan razvoj metode multimodalne hromatografije primenom principa ugrađivanja kvaliteta kroz dizajn za analizu odabarnih lekova
VL  - 72
IS  - 4 suplement
SP  - S243
EP  - S244
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4524
ER  - 

@conference{
author = "Svrkota, Bojana and Krmar, Jovana and Protić, Ana and Otašević, Biljana",
year = "2022",
abstract = "Mixed-Mode Liquid Chromatography (MMLC) includes several separation
mechanisms in a single column, which is why MMLC can analyze compounds in a broad
range of polarities and ionization potentials in a single run (1). Acclaim Mixed-Mode WCX-1
column with the ability to expose hydrophobic and weak cation exchange interactions was
thus selected to analyse a challenging mixture of neutral and cationic forms: ergotamine,
mecloxamine, camylofin, caffeine and propyphenazone, used as a fixed combination. MMLC
method was developed in line with Analytical Quality by Design (AQbD) approach implying
the scientifically-based understanding of process properties and risk-based management of
the method life cycle. AQbD refers to pre-definition of the method’s Analytical Target Profile
(ATP) by means of baseline separations within the shortest possible time, as well as
definition of Critical Method Attributes (CMAs) as a measure of method quality and Critical
Method Parameters (CMPs) affecting CMAs (2). Acetonitrile content, pH and acetate buffer
concentration were selected as CMPs since retention mechanism expression in MMLC
strongly depends on the mobile phase characteristics. The dependence of CMAs on CMPs was
revealed following a face-centred central composition design plan of experiments and
accompanying mathematical models, coefficients and standard error values. Design Space in
which ATP is achieved with a high level of reliability (π = 90%), was determined by Monte
Carlo simulations taking error distribution into account. Its margins pointed out to the
working point that assures proper method robustness (pH 5.2, 90 mM acetate buffer solution
and 48% (v/v) of acetonitrile)., Multimodalna tečna hromatografija (Mixed‐Mode Liquid Chromatography – MMLC)
uključuje nekoliko mehanizama razdvajanja u jednoj koloni, zbog čega se ova tehnika može
koristiti za simultanu analizu jedinjenja širokog opsega polarnosti i jonizacionog potencijala
(1). Acclaim Mixed‐Mode WCX‐1 kolona sa sposobnošću ekspresije hidrofobnih i interakcija
slabe katjonske izmene, je odabrana za analizu izazovne smeše neutralnih i katjonskih oblika
analita: ergotamina, mekloksamina, kamilofina, kofeina i propifenazona, koji se primenjuju u
fiksnoj kombinaciji. MMLC metoda je razvijena u skladu sa pristupom ugradnje kvaliteta kroz
dizajn (Analytical Quality by Design – AQbD) koji podrazumeva naučno zasnovano
razumevanje svojstava procesa i upravljanje životnim ciklusom metode prema riziku. AQbD
se odnosi na unapred definisanje analitičkog ciljanog profila metode (Analytical Target
Profile - ATP) odnosno razdvajanje na baznoj liniji za što kraće vreme, kao i na definisanje
kritičnih osobina metode (Critical Method Attributes - CMA) kao mere kvaliteta metode i
kritičnih parametara metode (Critical Method Parameters - CMP) koji utiču na CMA (2).
Sadržaj acetonitrila, pH i koncentracija acetatnog pufera izabrani su kao CMP, pošto
ekspresija MMLC retencionih mehanizma zavisi od karakteristika mobilne faze. Zavisnost
CMA od CMP definisana je pomoću plana eksperimenata usklađenim sa centralnim
kompozicionim dizajnom, ka centru orijentisanim i pratećim matematičkim modelima,
koeficijentima i vrednostima standardne greške. Prostor dizajna u kome se ATP postiže sa
visokim nivoom pouzdanosti (π = 90%) određen je Monte Karlo simulacijama uzimajuć i u
obzir distribuciju grešaka. Njegov okvir ukazuje na radnu tačku koja obezbeđuje
odgovarajuć u robusnost metode (pH 5,2, 90 mM rastvor acetatnog pufera i 48% (v/v)
acetonitrila).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Robust mixed-mode chromatography method development using Analytical Quality by Design approach for analysis of selected drugs, Robustan razvoj metode multimodalne hromatografije primenom principa ugrađivanja kvaliteta kroz dizajn za analizu odabarnih lekova",
volume = "72",
number = "4 suplement",
pages = "S243-S244",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4524"
}

Svrkota, B., Krmar, J., Protić, A.,& Otašević, B.. (2022). Robust mixed-mode chromatography method development using Analytical Quality by Design approach for analysis of selected drugs. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S243-S244.
https://hdl.handle.net/21.15107/rcub_farfar_4524

Svrkota B, Krmar J, Protić A, Otašević B. Robust mixed-mode chromatography method development using Analytical Quality by Design approach for analysis of selected drugs. in Arhiv za farmaciju. 2022;72(4 suplement):S243-S244.
https://hdl.handle.net/21.15107/rcub_farfar_4524 .

Svrkota, Bojana, Krmar, Jovana, Protić, Ana, Otašević, Biljana, "Robust mixed-mode chromatography method development using Analytical Quality by Design approach for analysis of selected drugs" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S243-S244,
https://hdl.handle.net/21.15107/rcub_farfar_4524 .

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  - Đajić, Nevena
AU  - Krmar, Jovana
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4694
AB  - Introduction: Cyclodextrin (CD) added to RPHPLC
mobile phase interacts with analytes,
solvent components and stationary phase surface.
Therefore, the retention is influenced by the
analyte’s distribution between CD dissolved in the
mobile phase, free CD and formed inclusion
complex adsorbed onto the stationary phase, and
stationary phase itself (1, 2). The research goal
was to reveal the structural characteristics affecting
the inclusion complexation and retention in these
kinds of chromatographic systems by employing
QSRR-ANN models. Materials and Methods: Mixed QSRR model
included large pool of molecular descriptors,
complex association constants and experimental
parameters towards the retention factor of
risperidone, olanzapine and structurally related
impurities. The experimental space was
adequately covered with central composite design,
while experiments were conducted on Dionex
Ultimate 3000 (U) HPLC. QSRR-ANN modelling
was performed in STATISTICA Neural Networks.
Results: To evaluate the individual influence of
each of the descriptors, the difference in the
highest and lowest retention factor value across
the investigated range of the descriptor’s values
was calculated. The highest ratios were associated
with the following descriptors RDF075m, UE,
Mor04v and CATS2D_08_PL, making them the
most contributing towards the selected output.
RDF075m descriptor shows the three-dimensional
mass distribution calculated at a distance of 7.5 Å
from the geometrical centre of the molecule and it
refers to steric factors at the same distance.
Groups approximately 7.5 Å distant from the
geometrical centre of risperidone, olanzapine and
related compounds in their optimized
conformations were determined. These groups
were the same ones involved in the complexation
process according to previously performed NMR
study. Identified groups and their steric factors are
the most important for the formation of inclusion
complexes, and, in this way, the value of RDF075m
contributes to the retention of the selected
compounds. The importance of Mor04v confirms
the influence of molecular size and shape in
retention in these kinds of chromatographic
systems, while CATS2D_08_PL accounts for
lipophilicity.
Conclusions: The current study resulted in
development of QSRR-ANN with remarkable
performances, which enabled the elucidation of the
molecular features significantly influencing the
retention in β-CD-modified RP-HPLC. The
pronounced effect of molecular structure on
retention was best described through RDF075m,
followed by UE, Mor04v and CATS2D_08_PL.
Retention behaviour is also highly affected by
molecular size and shape, as well as lipophilicity of
the investigated compounds. Moreover, the size
and polarity of the chosen CD should not be
neglected, due to the consequent structural fit.
PB  - Ankara University Faculty of Pharmacy
C3  - The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event
T1  - QSRR-ANN modelling in β-CD-modified RP-HPLC
SP  - 104
EP  - 105
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4694
ER  - 

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

Đajić, N., Krmar, J., Otašević, B., Malenović, A.,& Protić, A.. (2021). QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event
Ankara University Faculty of Pharmacy., 104-105.
https://hdl.handle.net/21.15107/rcub_farfar_4694

Đajić N, Krmar J, Otašević B, Malenović A, Protić A. QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event. 2021;:104-105.
https://hdl.handle.net/21.15107/rcub_farfar_4694 .

Đajić, Nevena, Krmar, Jovana, Otašević, Biljana, Malenović, Anđelija, Protić, Ana, "QSRR-ANN modelling in β-CD-modified RP-HPLC" in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event (2021):104-105,
https://hdl.handle.net/21.15107/rcub_farfar_4694 .

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 .