TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Čakar, Mira
AU  - Todorović, Nina
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5589
AB  - The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene
hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in
methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04)
defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the
distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M
HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and
polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a
concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility
of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10–
3 M HP–β-CD which
was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of
10–
3 M β-CD.
PB  - Springer Nature
T2  - Chemical Papers
T1  - Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride
DO  - 10.1007/s11696-024-03399-1
ER  - 

@article{
author = "Popović-Nikolić, Marija and Čakar, Mira and Todorović, Nina and Nikolić, Katarina and Popović, Gordana",
year = "2024",
abstract = "The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene
hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in
methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04)
defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the
distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M
HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and
polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a
concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility
of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10–
3 M HP–β-CD which
was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of
10–
3 M β-CD.",
publisher = "Springer Nature",
journal = "Chemical Papers",
title = "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride",
doi = "10.1007/s11696-024-03399-1"
}

Popović-Nikolić, M., Čakar, M., Todorović, N., Nikolić, K.,& Popović, G.. (2024). Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers
Springer Nature..
https://doi.org/10.1007/s11696-024-03399-1

Popović-Nikolić M, Čakar M, Todorović N, Nikolić K, Popović G. Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers. 2024;.
doi:10.1007/s11696-024-03399-1 .

Popović-Nikolić, Marija, Čakar, Mira, Todorović, Nina, Nikolić, Katarina, Popović, Gordana, "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride" in Chemical Papers (2024),
https://doi.org/10.1007/s11696-024-03399-1 . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5045
AB  - The protolytic equilibria of bilastine were studied experimentally and theoretically. The
pKa values were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and
temperature 25 °C. Energy calculation of the optimized structures of the equilibrium forms was
performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of
the theoretical study helped to define the ionization profile of bilastine and to assign the
experimentally determined pKa values to the corresponding ionizable groups.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - Theoretical and experimental study of bilastine ionization
SP  - 427
EP  - 430
DO  - 10.46793/ICCBI23.427PN
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "The protolytic equilibria of bilastine were studied experimentally and theoretically. The
pKa values were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and
temperature 25 °C. Energy calculation of the optimized structures of the equilibrium forms was
performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of
the theoretical study helped to define the ionization profile of bilastine and to assign the
experimentally determined pKa values to the corresponding ionizable groups.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "Theoretical and experimental study of bilastine ionization",
pages = "427-430",
doi = "10.46793/ICCBI23.427PN"
}

Popović-Nikolić, M., Popović, G., Oljačić, S.,& Nikolić, K.. (2023). Theoretical and experimental study of bilastine ionization. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 427-430.
https://doi.org/10.46793/ICCBI23.427PN

Popović-Nikolić M, Popović G, Oljačić S, Nikolić K. Theoretical and experimental study of bilastine ionization. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:427-430.
doi:10.46793/ICCBI23.427PN .

Popović-Nikolić, Marija, Popović, Gordana, Oljačić, Slavica, Nikolić, Katarina, "Theoretical and experimental study of bilastine ionization" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):427-430,
https://doi.org/10.46793/ICCBI23.427PN . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Aleksić, Mara
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5044
AB  - he redox properties of two quinoxaline derivatives, brimonidine and varenicline,
previously studied electrochemically, were evaluated by performing a computational study. On
the basis of some useful quantum chemical parameters the differences and similarities between
their redox features were explained. The obtained results support the experimental findings that
the redox processes of both compounds are under strong influence of the solution pH, whereas
the reduction of brimonidine occurs easier than the reduction of varenicline, at corresponding pH
values.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - DFT approach of the redox properties of brimonidine and varenicline
SP  - 423
EP  - 426
DO  - 10.46793/ICCBI23.423PN
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Nikolić, Katarina and Aleksić, Mara",
year = "2023",
abstract = "he redox properties of two quinoxaline derivatives, brimonidine and varenicline,
previously studied electrochemically, were evaluated by performing a computational study. On
the basis of some useful quantum chemical parameters the differences and similarities between
their redox features were explained. The obtained results support the experimental findings that
the redox processes of both compounds are under strong influence of the solution pH, whereas
the reduction of brimonidine occurs easier than the reduction of varenicline, at corresponding pH
values.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "DFT approach of the redox properties of brimonidine and varenicline",
pages = "423-426",
doi = "10.46793/ICCBI23.423PN"
}

Popović-Nikolić, M., Nikolić, K.,& Aleksić, M.. (2023). DFT approach of the redox properties of brimonidine and varenicline. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 423-426.
https://doi.org/10.46793/ICCBI23.423PN

Popović-Nikolić M, Nikolić K, Aleksić M. DFT approach of the redox properties of brimonidine and varenicline. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:423-426.
doi:10.46793/ICCBI23.423PN .

Popović-Nikolić, Marija, Nikolić, Katarina, Aleksić, Mara, "DFT approach of the redox properties of brimonidine and varenicline" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):423-426,
https://doi.org/10.46793/ICCBI23.423PN . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Popović, Gordana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5013
PB  - European Research Network on Signal Transduction CA18133
C3  - 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event
T1  - The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems
SP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5013
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Popović, Gordana and Nikolić, Katarina",
year = "2023",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event",
title = "The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5013"
}

Popović-Nikolić, M., Oljačić, S., Popović, G.,& Nikolić, K.. (2023). The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems. in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event
European Research Network on Signal Transduction CA18133., 35.
https://hdl.handle.net/21.15107/rcub_farfar_5013

Popović-Nikolić M, Oljačić S, Popović G, Nikolić K. The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems. in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event. 2023;:35.
https://hdl.handle.net/21.15107/rcub_farfar_5013 .

Popović-Nikolić, Marija, Oljačić, Slavica, Popović, Gordana, Nikolić, Katarina, "The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems" in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event (2023):35,
https://hdl.handle.net/21.15107/rcub_farfar_5013 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5004
AB  - Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults
as well as in pediatric patients 6 months of age and older. Because it is associated with
numerous side effects, including neuropsychiatric events, it is very important to monitor its
pharmacologic behavior when administered chronically. To gain better insight into the
pharmacological properties of ionizable drugs, their physicochemical properties should be
studied under conditions more similar to physiological, such as micellar solutions of
surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic
(carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar
solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX-
100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems
SP  - 49
EP  - 49
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5004
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina and Popović, Gordana",
year = "2023",
abstract = "Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults
as well as in pediatric patients 6 months of age and older. Because it is associated with
numerous side effects, including neuropsychiatric events, it is very important to monitor its
pharmacologic behavior when administered chronically. To gain better insight into the
pharmacological properties of ionizable drugs, their physicochemical properties should be
studied under conditions more similar to physiological, such as micellar solutions of
surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic
(carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar
solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX-
100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems",
pages = "49-49",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5004"
}

Popović-Nikolić, M., Oljačić, S., Nikolić, K.,& Popović, G.. (2023). Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 49-49.
https://hdl.handle.net/21.15107/rcub_farfar_5004

Popović-Nikolić M, Oljačić S, Nikolić K, Popović G. Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:49-49.
https://hdl.handle.net/21.15107/rcub_farfar_5004 .

Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, Popović, Gordana, "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):49-49,
https://hdl.handle.net/21.15107/rcub_farfar_5004 .

TY  - CONF
AU  - Obradović, Darija
AU  - Komsta, Lukasz
AU  - Popović-Nikolić, Marija
AU  - Milutinović, Jovana
AU  - Lazović, Saša
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5002
AB  - Most biomimetic chromatography measurements provide information on the ability of
drugs to pass through cell membranes, their interaction with protein-based structures and
distribution properties. The biomimetic properties of thin-layer chromatography (TLC)
conditions have not been investigated so far. In our previous research, the presence of dual
retention mechanisms for selected imidazoline and serotonin receptor ligands was
confirmed under TLC conditions on C-18, diol, and a silica-based phases. The mobile phase
was amixture of ACN and water with 20 mM ammoniumacetate and 0.1 volume %of acetic
acid [1]. In this research, the average retention parameters were determined by using the
integration procedure [2]. The parameter RMH is the average retention in the hydrophilicdominated
(HILIC), while RMR is the average retention in the region of reversed-phase
interactions (RP). The parameter RMA corresponds to the average retention within the
overall HILIC/RP region. The lipophilicity successfully correlates with the C-18 and silica
based behaviour. For plasma protein binding affinity, the best correlations were found
within C-18 and silica-based systems (r > 0.70). There is also a correlation of average silica
gel and C-18 mechanism of interaction with the volume of distribution (r > 0.73), and the
intestinal absorption (r > 0.70). The retention behaviour on the diol phase showed a good
correlation with the P-gp inhibitor activity (r = 0.80). TLC systems that provide dual
retention mechanisms can be successfully used in the rapid biomimetic profiling of
serotonin and imidazoline receptor ligands in the first steps of drug discovery.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting, Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Biomimetic characteristics of dual TLC retention mechanism
SP  - 48
EP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5002
ER  - 

@conference{
author = "Obradović, Darija and Komsta, Lukasz and Popović-Nikolić, Marija and Milutinović, Jovana and Lazović, Saša",
year = "2023",
abstract = "Most biomimetic chromatography measurements provide information on the ability of
drugs to pass through cell membranes, their interaction with protein-based structures and
distribution properties. The biomimetic properties of thin-layer chromatography (TLC)
conditions have not been investigated so far. In our previous research, the presence of dual
retention mechanisms for selected imidazoline and serotonin receptor ligands was
confirmed under TLC conditions on C-18, diol, and a silica-based phases. The mobile phase
was amixture of ACN and water with 20 mM ammoniumacetate and 0.1 volume %of acetic
acid [1]. In this research, the average retention parameters were determined by using the
integration procedure [2]. The parameter RMH is the average retention in the hydrophilicdominated
(HILIC), while RMR is the average retention in the region of reversed-phase
interactions (RP). The parameter RMA corresponds to the average retention within the
overall HILIC/RP region. The lipophilicity successfully correlates with the C-18 and silica
based behaviour. For plasma protein binding affinity, the best correlations were found
within C-18 and silica-based systems (r > 0.70). There is also a correlation of average silica
gel and C-18 mechanism of interaction with the volume of distribution (r > 0.73), and the
intestinal absorption (r > 0.70). The retention behaviour on the diol phase showed a good
correlation with the P-gp inhibitor activity (r = 0.80). TLC systems that provide dual
retention mechanisms can be successfully used in the rapid biomimetic profiling of
serotonin and imidazoline receptor ligands in the first steps of drug discovery.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting, Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Biomimetic characteristics of dual TLC retention mechanism",
pages = "48-48",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5002"
}

Obradović, D., Komsta, L., Popović-Nikolić, M., Milutinović, J.,& Lazović, S.. (2023). Biomimetic characteristics of dual TLC retention mechanism. in 10th IAPC Meeting, Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 48-48.
https://hdl.handle.net/21.15107/rcub_farfar_5002

Obradović D, Komsta L, Popović-Nikolić M, Milutinović J, Lazović S. Biomimetic characteristics of dual TLC retention mechanism. in 10th IAPC Meeting, Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:48-48.
https://hdl.handle.net/21.15107/rcub_farfar_5002 .

Obradović, Darija, Komsta, Lukasz, Popović-Nikolić, Marija, Milutinović, Jovana, Lazović, Saša, "Biomimetic characteristics of dual TLC retention mechanism" in 10th IAPC Meeting, Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):48-48,
https://hdl.handle.net/21.15107/rcub_farfar_5002 .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4687
AB  - The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and rami-
pril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically
determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the
computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa ) determined in micellar media in relation
to the pKa values previously determined in “pure” water, the effect of Brij 35 micelles on ACEIs ionization was estimated.
The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs
(ΔpKa from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular
form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs
and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that
ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which
potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium
forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes
biopharmaceutically important pH values.
PB  - Springer
T2  - Monatshefte für Chemie - Chemical Monthly
T1  - Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35
VL  - 154
SP  - 615
EP  - 624
DO  - 10.1007/s00706-023-03059-2
ER  - 

@article{
author = "Popović-Nikolić, Marija and Nikolić, Katarina and Popović, Gordana",
year = "2023",
abstract = "The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and rami-
pril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically
determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the
computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa ) determined in micellar media in relation
to the pKa values previously determined in “pure” water, the effect of Brij 35 micelles on ACEIs ionization was estimated.
The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs
(ΔpKa from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular
form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs
and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that
ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which
potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium
forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes
biopharmaceutically important pH values.",
publisher = "Springer",
journal = "Monatshefte für Chemie - Chemical Monthly",
title = "Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35",
volume = "154",
pages = "615-624",
doi = "10.1007/s00706-023-03059-2"
}

Popović-Nikolić, M., Nikolić, K.,& Popović, G.. (2023). Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35. in Monatshefte für Chemie - Chemical Monthly
Springer., 154, 615-624.
https://doi.org/10.1007/s00706-023-03059-2

Popović-Nikolić M, Nikolić K, Popović G. Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35. in Monatshefte für Chemie - Chemical Monthly. 2023;154:615-624.
doi:10.1007/s00706-023-03059-2 .

Popović-Nikolić, Marija, Nikolić, Katarina, Popović, Gordana, "Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35" in Monatshefte für Chemie - Chemical Monthly, 154 (2023):615-624,
https://doi.org/10.1007/s00706-023-03059-2 . .

TY  - CONF
AU  - Čarapić, Marija
AU  - Petković, Miloš
AU  - Marković, Bojan
AU  - Popović-Nikolić, Marija
AU  - Agbaba, Danica
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4684
AB  - Ziprasidone (ZIP) is the second generation antipsychotic drug with unique G-protein-coupled
(GPCR) receptor binding profile. It is a highly lipophilic and unstable compound. Our group
developed and validated the single liquid chromatographic (LC) system for simultaneous
determination of ZIP and its five main impurities (IMPs) and we modelled the Quantitative
Structure Retention Relationship (QSRR) of the additional ten compounds including unknown
detected degradant. One of two proposed structures were confirmed by UPLC-MS/MS study. The
further characterisation of unknown degradant was performed with NMR studies as un versatile
tool for characterisation of each compound and it is presented. Through several experiments which consists of investigation of chemical shitfs in NMR spectra of ZIP degradation products the
structure of unknown degradant was proposed and confirmed as in previous experiments.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
T1  - Characterization of unknown degradant of ziprasidone with NMR spetroscopy
VL  - II
SP  - 601
EP  - 604
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4684
ER  - 

@conference{
author = "Čarapić, Marija and Petković, Miloš and Marković, Bojan and Popović-Nikolić, Marija and Agbaba, Danica and Nikolić, Katarina",
year = "2022",
abstract = "Ziprasidone (ZIP) is the second generation antipsychotic drug with unique G-protein-coupled
(GPCR) receptor binding profile. It is a highly lipophilic and unstable compound. Our group
developed and validated the single liquid chromatographic (LC) system for simultaneous
determination of ZIP and its five main impurities (IMPs) and we modelled the Quantitative
Structure Retention Relationship (QSRR) of the additional ten compounds including unknown
detected degradant. One of two proposed structures were confirmed by UPLC-MS/MS study. The
further characterisation of unknown degradant was performed with NMR studies as un versatile
tool for characterisation of each compound and it is presented. Through several experiments which consists of investigation of chemical shitfs in NMR spectra of ZIP degradation products the
structure of unknown degradant was proposed and confirmed as in previous experiments.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)",
title = "Characterization of unknown degradant of ziprasidone with NMR spetroscopy",
volume = "II",
pages = "601-604",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4684"
}

Čarapić, M., Petković, M., Marković, B., Popović-Nikolić, M., Agbaba, D.,& Nikolić, K.. (2022). Characterization of unknown degradant of ziprasidone with NMR spetroscopy. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., II, 601-604.
https://hdl.handle.net/21.15107/rcub_farfar_4684

Čarapić M, Petković M, Marković B, Popović-Nikolić M, Agbaba D, Nikolić K. Characterization of unknown degradant of ziprasidone with NMR spetroscopy. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings). 2022;II:601-604.
https://hdl.handle.net/21.15107/rcub_farfar_4684 .

Čarapić, Marija, Petković, Miloš, Marković, Bojan, Popović-Nikolić, Marija, Agbaba, Danica, Nikolić, Katarina, "Characterization of unknown degradant of ziprasidone with NMR spetroscopy" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings), II (2022):601-604,
https://hdl.handle.net/21.15107/rcub_farfar_4684 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Mudrić, Jelena
AU  - Popović, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4683
AB  - The ionization constants (pKa) of ceftazidime, third generation cephalosporin, were determined by potentiometry. Ceftazidime is an ampholyte with four ionizable centers, three acidic centers (two carboxyl groups and amide group) and one basic center (aminothiazole). Potentiometric determinations were performed at 25 °C and constant ionic strength of 0.1 M (NaCl). Experimental data were analyzed by computer software Hyperquad and four pKa values were derived: pKa1 2.55; pKa2 3.94; pKa3 4.54 and pKa4 7.55. According to the obtained pKa values distribution diagram as a function of pH was constructed and distribution of the ceftazidime equilibrium forms was calculated at a pH values of biopharmaceutical significance (pH 1.2, 4.5, 6.8 and 7.4). In addition, based on the chemical structure of ceftazidime the order of ionization were suggested.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
T1  - The determination of the ionization profile of ceftazidime
VL  - II
SP  - 585
EP  - 588
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4683
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Mudrić, Jelena and Popović, Gordana",
year = "2022",
abstract = "The ionization constants (pKa) of ceftazidime, third generation cephalosporin, were determined by potentiometry. Ceftazidime is an ampholyte with four ionizable centers, three acidic centers (two carboxyl groups and amide group) and one basic center (aminothiazole). Potentiometric determinations were performed at 25 °C and constant ionic strength of 0.1 M (NaCl). Experimental data were analyzed by computer software Hyperquad and four pKa values were derived: pKa1 2.55; pKa2 3.94; pKa3 4.54 and pKa4 7.55. According to the obtained pKa values distribution diagram as a function of pH was constructed and distribution of the ceftazidime equilibrium forms was calculated at a pH values of biopharmaceutical significance (pH 1.2, 4.5, 6.8 and 7.4). In addition, based on the chemical structure of ceftazidime the order of ionization were suggested.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)",
title = "The determination of the ionization profile of ceftazidime",
volume = "II",
pages = "585-588",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4683"
}

Popović-Nikolić, M., Mudrić, J.,& Popović, G.. (2022). The determination of the ionization profile of ceftazidime. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., II, 585-588.
https://hdl.handle.net/21.15107/rcub_farfar_4683

Popović-Nikolić M, Mudrić J, Popović G. The determination of the ionization profile of ceftazidime. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings). 2022;II:585-588.
https://hdl.handle.net/21.15107/rcub_farfar_4683 .

Popović-Nikolić, Marija, Mudrić, Jelena, Popović, Gordana, "The determination of the ionization profile of ceftazidime" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings), II (2022):585-588,
https://hdl.handle.net/21.15107/rcub_farfar_4683 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Čakar, Mira
AU  - Popović, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4682
AB  - The apparent ionization constants (pKa*) of raloxifene have been determined potentiometrically in methanol water mixtures (45% - 55% wt/wt) and the pKa values (pKa1=7.21±0.02, pKa2=7.86±0.02, pKa3=9.97±0.04) which define the ionization in aqueous media were obtained by extrapolation of the pKa* values to 0% of methanol. Obtained pKa values were assigned to corresponding ionization centers. On the basis of the ionization constants determined in this study distribution of raloxifene equilibrium forms have been calculated.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
T1  - The protolytic equilibria of raloxifene
VL  - II
SP  - 581
EP  - 584
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4682
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Čakar, Mira and Popović, Gordana",
year = "2022",
abstract = "The apparent ionization constants (pKa*) of raloxifene have been determined potentiometrically in methanol water mixtures (45% - 55% wt/wt) and the pKa values (pKa1=7.21±0.02, pKa2=7.86±0.02, pKa3=9.97±0.04) which define the ionization in aqueous media were obtained by extrapolation of the pKa* values to 0% of methanol. Obtained pKa values were assigned to corresponding ionization centers. On the basis of the ionization constants determined in this study distribution of raloxifene equilibrium forms have been calculated.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)",
title = "The protolytic equilibria of raloxifene",
volume = "II",
pages = "581-584",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4682"
}

Popović-Nikolić, M., Čakar, M.,& Popović, G.. (2022). The protolytic equilibria of raloxifene. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings)
Society of Physical Chemists of Serbia., II, 581-584.
https://hdl.handle.net/21.15107/rcub_farfar_4682

Popović-Nikolić M, Čakar M, Popović G. The protolytic equilibria of raloxifene. in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings). 2022;II:581-584.
https://hdl.handle.net/21.15107/rcub_farfar_4682 .

Popović-Nikolić, Marija, Čakar, Mira, Popović, Gordana, "The protolytic equilibria of raloxifene" in PHYSICAL CHEMISTRY 2022, 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry (Proceedings), II (2022):581-584,
https://hdl.handle.net/21.15107/rcub_farfar_4682 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4597
AB  - The knowledge of drugs ionization is necessary for prediction of their pharmacological
behavior and pharmacokinetic parameters (1). However, the distribution of equilibrium forms
could differ from expected one if the estimation is made exclusively based on pKa vales observed
in “pure” water. It is necessary to investigate the ionization of drugs in conditions which is known
to mimic the biological membranes such as the micellar solutions of surfactants (2). The pKa
values of pharmacologically active compounds (antihypertensives, antimicrobial drugs,
antihistamines) have been potentiometrically determined under the same conditions (25 °C, ionic
strength 0.1 M NaCl) with and without micelles, anionic (SDS), cationic (CTAB), nonionic (TX-
100, Brij 35). Experimental results were analyzed in program Hyperquad. Significant shift in
protolytic equilibria (∆pKa) were observed for aliphatic amino (-2.80 to +0.87), aromatic amino (-
1.99 to +1.44), and carboxylic (-0.92 to +1.90) functional groups. The anionic and cationic
expressed higher effect on ionization comparing to nonionic micelles. The presence of micelles
caused the change in distribution of equilibrium forms especially on pH values of
biopharmaceutical importance where the content of ionized form was changed in range from -74%
to +66% comparing to “pure” water. The ionization groups of drugs are involved in interactions
with charged or polar surface of micelles which could be observed in terms of physiological
conditions. Result showed that general pattern of ionization of drugs in micellar media could not
be anticipated so it is necessary to be experimentally investigated for each individual drug.
AB  - Ispitivanje jonizacije lekova neophodno je za predviđanje farmakološkog ponašanja i
farmakokinetičkih parametara (1). Međutim, raspodela ravnotežnih oblika može biti
drugačija od očekivane ako se procena izvodi samo na osnovu pKa vrednosti definisanih
isključivo u “čistoj” vodi. Zato je potrebno ispitati jonizaciju lekova i u uslovima koji
simuliraju prisustvo bioloških membrana, kao što su micelarni rastvori surfaktanata (2). U
ovoj studiji, pKa vrednosti farmakološki aktivnih jedinjenja (antihipertenzivi, antimikrobni
lekovi, antihistaminici), bez i u prisustvu anjonskih (SDS), katjonskih (CTAB) i nejonskih (TX-
100, Brij 35) micela, određene su potenciometrijski, pod istim eksperimentalnim uslovima
(temperatura 25°C i jonska sila 0,1 M NaCl). Eksperimentalni rezultati analizirani su u
programu Hyperquad. Značajna pomeranja protolitičkih ravnoteža (∆pKa) uočena su u
slučaju aromatične amino (od -1,99 do +1,44), alifatične amino (od -2,80 do +0,87) i
karboksilne grupe (od -0,92 do +1,90). Izraženiji uticaj na promenu jonizacije uočen je u
prisustvu anjonskih i katjonskih u odnosu na nejonske micele. Promena raspodele
ravnotežnih oblika u prisustvu micela zapažena je na biofarmaceutski značajnim pH
vrednostima (1,2; 4,5; 6,8; 7,4), pri čemu je sadržaj jonizovanih formi promenjen u opsegu od
-74% do +66% u odnosu na “čistu” vodu. Rezultati pokazuju da se jonizacione grupe lekova
uključuju u interakcije sa polarnom ili naelektrisanom površinom micela što se može
potencijalno razmatrati u kontekstu uticaja na jonizaciju u fiziološkom uslovima. Nije uočen
uopšten obrazac jonizacije lekova u micelarnoj sredini iz čega sledi da je neophodno
eksperimentalno ispitati jonizaciju svakog pojedinačnog jedinjenja u prisustvu micela.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - The ionization of pharmacologically active compounds in the presence of differently charged micelles as biomembrane mimetic systems
T1  - Jonizacija farmakološki aktivnih jedinjenja u micelarnim rastvorima različitog naelektrisanja kao simulirajućih sistema biomembrana
VL  - 72
IS  - 4 suplement
SP  - S530
EP  - S531
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4597
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Nikolić, Katarina and Popović, Gordana",
year = "2022",
abstract = "The knowledge of drugs ionization is necessary for prediction of their pharmacological
behavior and pharmacokinetic parameters (1). However, the distribution of equilibrium forms
could differ from expected one if the estimation is made exclusively based on pKa vales observed
in “pure” water. It is necessary to investigate the ionization of drugs in conditions which is known
to mimic the biological membranes such as the micellar solutions of surfactants (2). The pKa
values of pharmacologically active compounds (antihypertensives, antimicrobial drugs,
antihistamines) have been potentiometrically determined under the same conditions (25 °C, ionic
strength 0.1 M NaCl) with and without micelles, anionic (SDS), cationic (CTAB), nonionic (TX-
100, Brij 35). Experimental results were analyzed in program Hyperquad. Significant shift in
protolytic equilibria (∆pKa) were observed for aliphatic amino (-2.80 to +0.87), aromatic amino (-
1.99 to +1.44), and carboxylic (-0.92 to +1.90) functional groups. The anionic and cationic
expressed higher effect on ionization comparing to nonionic micelles. The presence of micelles
caused the change in distribution of equilibrium forms especially on pH values of
biopharmaceutical importance where the content of ionized form was changed in range from -74%
to +66% comparing to “pure” water. The ionization groups of drugs are involved in interactions
with charged or polar surface of micelles which could be observed in terms of physiological
conditions. Result showed that general pattern of ionization of drugs in micellar media could not
be anticipated so it is necessary to be experimentally investigated for each individual drug., Ispitivanje jonizacije lekova neophodno je za predviđanje farmakološkog ponašanja i
farmakokinetičkih parametara (1). Međutim, raspodela ravnotežnih oblika može biti
drugačija od očekivane ako se procena izvodi samo na osnovu pKa vrednosti definisanih
isključivo u “čistoj” vodi. Zato je potrebno ispitati jonizaciju lekova i u uslovima koji
simuliraju prisustvo bioloških membrana, kao što su micelarni rastvori surfaktanata (2). U
ovoj studiji, pKa vrednosti farmakološki aktivnih jedinjenja (antihipertenzivi, antimikrobni
lekovi, antihistaminici), bez i u prisustvu anjonskih (SDS), katjonskih (CTAB) i nejonskih (TX-
100, Brij 35) micela, određene su potenciometrijski, pod istim eksperimentalnim uslovima
(temperatura 25°C i jonska sila 0,1 M NaCl). Eksperimentalni rezultati analizirani su u
programu Hyperquad. Značajna pomeranja protolitičkih ravnoteža (∆pKa) uočena su u
slučaju aromatične amino (od -1,99 do +1,44), alifatične amino (od -2,80 do +0,87) i
karboksilne grupe (od -0,92 do +1,90). Izraženiji uticaj na promenu jonizacije uočen je u
prisustvu anjonskih i katjonskih u odnosu na nejonske micele. Promena raspodele
ravnotežnih oblika u prisustvu micela zapažena je na biofarmaceutski značajnim pH
vrednostima (1,2; 4,5; 6,8; 7,4), pri čemu je sadržaj jonizovanih formi promenjen u opsegu od
-74% do +66% u odnosu na “čistu” vodu. Rezultati pokazuju da se jonizacione grupe lekova
uključuju u interakcije sa polarnom ili naelektrisanom površinom micela što se može
potencijalno razmatrati u kontekstu uticaja na jonizaciju u fiziološkom uslovima. Nije uočen
uopšten obrazac jonizacije lekova u micelarnoj sredini iz čega sledi da je neophodno
eksperimentalno ispitati jonizaciju svakog pojedinačnog jedinjenja u prisustvu micela.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "The ionization of pharmacologically active compounds in the presence of differently charged micelles as biomembrane mimetic systems, Jonizacija farmakološki aktivnih jedinjenja u micelarnim rastvorima različitog naelektrisanja kao simulirajućih sistema biomembrana",
volume = "72",
number = "4 suplement",
pages = "S530-S531",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4597"
}

Popović-Nikolić, M., Nikolić, K.,& Popović, G.. (2022). The ionization of pharmacologically active compounds in the presence of differently charged micelles as biomembrane mimetic systems. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S530-S531.
https://hdl.handle.net/21.15107/rcub_farfar_4597

Popović-Nikolić M, Nikolić K, Popović G. The ionization of pharmacologically active compounds in the presence of differently charged micelles as biomembrane mimetic systems. in Arhiv za farmaciju. 2022;72(4 suplement):S530-S531.
https://hdl.handle.net/21.15107/rcub_farfar_4597 .

Popović-Nikolić, Marija, Nikolić, Katarina, Popović, Gordana, "The ionization of pharmacologically active compounds in the presence of differently charged micelles as biomembrane mimetic systems" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S530-S531,
https://hdl.handle.net/21.15107/rcub_farfar_4597 .

TY  - JOUR
AU  - Obradović, Darija
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4045
AB  - The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by per- forming a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure reten- tion relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I- Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the phar- macokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches
VL  - 211
DO  - 10.1016/j.jpba.2022.114593
ER  - 

@article{
author = "Obradović, Darija and Radan, Milica and Đikić, Teodora and Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina",
year = "2022",
abstract = "The drug-human serum albumin binding interaction was evaluated on a stationary phase immobilized with human serum albumin using a mixture of phosphate buffer (pH 7.0) and acetonitrile modifier as mobile phase. The 33 compounds that have a wide structural and therapeutic diversity were analyzed by per- forming a large number of experiments. The interaction mechanism was interpreted based on: i) retention characteristics of structurally related compounds, ii) retention modeling, iii) quantitative structure reten- tion relationship (QSRR), and iv) molecular docking. Small structural differences of related compounds (e.g., reflected in different lipophilicity and polarity) have been found to affect their different binding to human serum albumin. It was found that drug retention in HSA column can be successfully described by using the quadratic function. The isocratic (logk(14%)) and extrapolated (b0(LSS)) retention factors showed the highest correlation (r > 0.76) with the constant that defines the binding affinity for human serum albumin (ACD/I- Lab). Therefore, selected chromatographic parameters can demonstrate reliable applicability for rapid screening of drug-plasma protein binding in drug discovery. In QSRR study, the resulting SVM/logk(14%) and MLR/b0(LSS) models display high internal and external predictive power. The constitutional properties (double bonds, aromatic rings, benzyl, allyl, -amino and -sulfur containing functional groups) supported by the charged parts of surface area had a significant impact on human serum albumin-binding affinity, which was also confirmed with molecular docking study. The high structural diversity of the data set provides wide applicability of tested chromatographic conditions and constructed models for defining the phar- macokinetic profile and possible structural modifications that can increase plasma protein binding of newly synthesized, pharmaceutically important compounds.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches",
volume = "211",
doi = "10.1016/j.jpba.2022.114593"
}

Obradović, D., Radan, M., Đikić, T., Popović-Nikolić, M., Oljačić, S.,& Nikolić, K.. (2022). The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 211.
https://doi.org/10.1016/j.jpba.2022.114593

Obradović D, Radan M, Đikić T, Popović-Nikolić M, Oljačić S, Nikolić K. The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches. in Journal of Pharmaceutical and Biomedical Analysis. 2022;211.
doi:10.1016/j.jpba.2022.114593 .

Obradović, Darija, Radan, Milica, Đikić, Teodora, Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, "The evaluation of drug-plasma protein binding interaction on immobilized human serum albumin stationary phase, aided by different computational approaches" in Journal of Pharmaceutical and Biomedical Analysis, 211 (2022),
https://doi.org/10.1016/j.jpba.2022.114593 . .

TY  - CONF
AU  - Obradović, Darija
AU  - Radan, Milica
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4686
AB  - The human serum albumin (HSA) is well known for its extraordinary binding capacity
for both endogenous and exogenous compounds, including a wide range of drugs. The goal of
our investigation was to evaluate the distribution process for 15 CNS active compounds. The
drug-plasma protein interaction was evaluated under simulative physiological conditions on the
HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and
acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to
approximate the % of protein-binding by calculating the P(%) values. The results obtained
through this study demonstrated that the constitutional properties (e.g. number of total bonds,
atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding
affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available
for the CYP450 oxidation showed the most significant correlation (r = 0.92). This study
provides a basis for further in vitro chromatographical investigations of drug-HSA interaction
for CNS active compounds. The correlation between obtained retention data and the availability
to enzymes oxidation indicates the application of the tested system in the assessment of the
metabolic degradation profile of CNS related drugs.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS)
T1  - The molecular basis of drug-plasma protein interaction for CNS active compounds
SP  - 375
EP  - 378
DO  - 10.46793/ICCBI21.375O
ER  - 

@conference{
author = "Obradović, Darija and Radan, Milica and Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina",
year = "2021",
abstract = "The human serum albumin (HSA) is well known for its extraordinary binding capacity
for both endogenous and exogenous compounds, including a wide range of drugs. The goal of
our investigation was to evaluate the distribution process for 15 CNS active compounds. The
drug-plasma protein interaction was evaluated under simulative physiological conditions on the
HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and
acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to
approximate the % of protein-binding by calculating the P(%) values. The results obtained
through this study demonstrated that the constitutional properties (e.g. number of total bonds,
atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding
affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available
for the CYP450 oxidation showed the most significant correlation (r = 0.92). This study
provides a basis for further in vitro chromatographical investigations of drug-HSA interaction
for CNS active compounds. The correlation between obtained retention data and the availability
to enzymes oxidation indicates the application of the tested system in the assessment of the
metabolic degradation profile of CNS related drugs.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS)",
title = "The molecular basis of drug-plasma protein interaction for CNS active compounds",
pages = "375-378",
doi = "10.46793/ICCBI21.375O"
}

Obradović, D., Radan, M., Popović-Nikolić, M., Oljačić, S.,& Nikolić, K.. (2021). The molecular basis of drug-plasma protein interaction for CNS active compounds. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS)
Institute for Information Technologies, University of Kragujevac, Serbia., 375-378.
https://doi.org/10.46793/ICCBI21.375O

Obradović D, Radan M, Popović-Nikolić M, Oljačić S, Nikolić K. The molecular basis of drug-plasma protein interaction for CNS active compounds. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS). 2021;:375-378.
doi:10.46793/ICCBI21.375O .

Obradović, Darija, Radan, Milica, Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, "The molecular basis of drug-plasma protein interaction for CNS active compounds" in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS) (2021):375-378,
https://doi.org/10.46793/ICCBI21.375O . .

TY  - CONF
AU  - Obradović, Darija
AU  - Oljačić, Slavica
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5190
AB  - Retention mechanism in the hydrophilic interaction liquid chromatography
(HILIC) mode is complex and still a subject of many controversial
interpretations. In order to describe the HILIC retention mechanism, different
retention models can be employed. In this study, we investigated the partition
mechanism for 7 imidazoline receptor ligands on the mixed mode HILIC
stationary phase. Applicability of the assumed retention model in description
of the HILIC retention behavior of the compounds was successfully
demonstrated.
PB  - Society of Physical Chemists of Serbia
C3  - Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - Investigation of retention behavior of imidazoline receptor ligands on mixedmode HILIC stationary phase
VL  - II
SP  - 1041
EP  - 1044
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5190
ER  - 

@conference{
author = "Obradović, Darija and Oljačić, Slavica and Popović-Nikolić, Marija and Popović, Gordana and Agbaba, Danica",
year = "2018",
abstract = "Retention mechanism in the hydrophilic interaction liquid chromatography
(HILIC) mode is complex and still a subject of many controversial
interpretations. In order to describe the HILIC retention mechanism, different
retention models can be employed. In this study, we investigated the partition
mechanism for 7 imidazoline receptor ligands on the mixed mode HILIC
stationary phase. Applicability of the assumed retention model in description
of the HILIC retention behavior of the compounds was successfully
demonstrated.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "Investigation of retention behavior of imidazoline receptor ligands on mixedmode HILIC stationary phase",
volume = "II",
pages = "1041-1044",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5190"
}

Obradović, D., Oljačić, S., Popović-Nikolić, M., Popović, G.,& Agbaba, D.. (2018). Investigation of retention behavior of imidazoline receptor ligands on mixedmode HILIC stationary phase. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., II, 1041-1044.
https://hdl.handle.net/21.15107/rcub_farfar_5190

Obradović D, Oljačić S, Popović-Nikolić M, Popović G, Agbaba D. Investigation of retention behavior of imidazoline receptor ligands on mixedmode HILIC stationary phase. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2018;II:1041-1044.
https://hdl.handle.net/21.15107/rcub_farfar_5190 .

Obradović, Darija, Oljačić, Slavica, Popović-Nikolić, Marija, Popović, Gordana, Agbaba, Danica, "Investigation of retention behavior of imidazoline receptor ligands on mixedmode HILIC stationary phase" in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, II (2018):1041-1044,
https://hdl.handle.net/21.15107/rcub_farfar_5190 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Berdon, Katarina
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5183
AB  - The pKa values of ciprofloxacin (CPF) and norfloxacin (NRF) were
determined potentiometrically, with and without the presence of differently
charged micelles, as biomembrane mimetic models. The shift in protolytic
equilibria are observed in the presence of surfactants, SDS (ΔpKa1 = +2.02;
ΔpKa2 = +0.57); CTAB (ΔpKa1 = -0.09; ΔpKa2 = -0.23) and TX-100 (ΔpKa1 =
+0.24; ΔpKa2 = +0.29). The change in distribution of equilibrium forms is
most expressed in pH range 6 – 8 which may indicate on potential interactions
with molecules of different polarity and charge under physiological
conditions.
PB  - Society of Physical Chemists of Serbia
C3  - Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - The ionization of fluoroquinolones in the presence of differently charged surfactants
VL  - II
SP  - 967
EP  - 970
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5183
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Berdon, Katarina",
year = "2018",
abstract = "The pKa values of ciprofloxacin (CPF) and norfloxacin (NRF) were
determined potentiometrically, with and without the presence of differently
charged micelles, as biomembrane mimetic models. The shift in protolytic
equilibria are observed in the presence of surfactants, SDS (ΔpKa1 = +2.02;
ΔpKa2 = +0.57); CTAB (ΔpKa1 = -0.09; ΔpKa2 = -0.23) and TX-100 (ΔpKa1 =
+0.24; ΔpKa2 = +0.29). The change in distribution of equilibrium forms is
most expressed in pH range 6 – 8 which may indicate on potential interactions
with molecules of different polarity and charge under physiological
conditions.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "The ionization of fluoroquinolones in the presence of differently charged surfactants",
volume = "II",
pages = "967-970",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5183"
}

Popović-Nikolić, M., Popović, G.,& Berdon, K.. (2018). The ionization of fluoroquinolones in the presence of differently charged surfactants. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., II, 967-970.
https://hdl.handle.net/21.15107/rcub_farfar_5183

Popović-Nikolić M, Popović G, Berdon K. The ionization of fluoroquinolones in the presence of differently charged surfactants. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2018;II:967-970.
https://hdl.handle.net/21.15107/rcub_farfar_5183 .

Popović-Nikolić, Marija, Popović, Gordana, Berdon, Katarina, "The ionization of fluoroquinolones in the presence of differently charged surfactants" in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, II (2018):967-970,
https://hdl.handle.net/21.15107/rcub_farfar_5183 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Stojilković, Kristina
AU  - Dobrosavljević, Maja
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5181
AB  - The pKa values of maleic and fumaric acid have been determined
potentiometrically in the presence and in the absence of differently charged
micelles. The ionization of maleic acid has been significantly affected (ΔpKa
up to 1.91) by the presence of micelles, unlike the ionization of fumaric acid
(ΔpKa up to +0.30). Observed shift in equilibrium forms is most expressed in
pH range 2 – 6.
PB  - Society of Physical Chemists of Serbia
C3  - Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
T1  - The effect of differently charged micelles on protolytic equilibria of maleic and fumaric acid
VL  - II
SP  - 931
EP  - 934
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5181
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Stojilković, Kristina and Dobrosavljević, Maja and Agbaba, Danica",
year = "2018",
abstract = "The pKa values of maleic and fumaric acid have been determined
potentiometrically in the presence and in the absence of differently charged
micelles. The ionization of maleic acid has been significantly affected (ΔpKa
up to 1.91) by the presence of micelles, unlike the ionization of fumaric acid
(ΔpKa up to +0.30). Observed shift in equilibrium forms is most expressed in
pH range 2 – 6.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry",
title = "The effect of differently charged micelles on protolytic equilibria of maleic and fumaric acid",
volume = "II",
pages = "931-934",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5181"
}

Popović-Nikolić, M., Popović, G., Stojilković, K., Dobrosavljević, M.,& Agbaba, D.. (2018). The effect of differently charged micelles on protolytic equilibria of maleic and fumaric acid. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry
Society of Physical Chemists of Serbia., II, 931-934.
https://hdl.handle.net/21.15107/rcub_farfar_5181

Popović-Nikolić M, Popović G, Stojilković K, Dobrosavljević M, Agbaba D. The effect of differently charged micelles on protolytic equilibria of maleic and fumaric acid. in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry. 2018;II:931-934.
https://hdl.handle.net/21.15107/rcub_farfar_5181 .

Popović-Nikolić, Marija, Popović, Gordana, Stojilković, Kristina, Dobrosavljević, Maja, Agbaba, Danica, "The effect of differently charged micelles on protolytic equilibria of maleic and fumaric acid" in Physical Chemistry 2018 (Proceedings) 14th International Conference on Fundamental and Applied Aspects of Physical Chemistry, II (2018):931-934,
https://hdl.handle.net/21.15107/rcub_farfar_5181 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Stojilković, Kristina
AU  - Dobrosavljević, Maja
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4879
AB  - Rupatadin je selektivni antagonist histaminskih H1 receptora druge generacije
koji se primenjuje u terapiji alergijskog rinitisa i hronične urtikarije. Rupatadin sadrži
tri jonizaciona centra, dva aromatična amina i jedan cikličan alkilamin. Dozirani
farmaceutski oblici za oralnu primenu kao aktivnu supstancu sadrže rupatadin fumarat.
U rastvoru rupatadin fumarata uspostavlja se složen sistem protolitičkih ravnoteža koji
uključuje tri bazna centra rupatadina i dve karboksilne grupe fumarne kiseline.
Poznavanje pKa vrednosti lekova neophodno je za procenu farmakokinetičkih osobina i
bioraspoloživosti. U fiziološkim uslovima pKa vrednosti mogu biti promenjene u odnosu
na vodeni rastvor usled interakcija sa naelektrisanim i polarnim biomolekulima.
Ispitivanje jonizacije u pojednostavljenim sistemima biomembrana, kao što su
micelarni rastvori surfaktanata, pruža bolji uvid u ponašanje lekova u fiziološkim
uslovima. Ispitan je uticaj micelarnih rastvora, anjonskog natrijum‐dodecilsulfata (SDS),
katjonskog cetiltrimetilamonijum‐bromida (CTAB) i nejonskog 4‐oktilfenol
polietoksilata (TX‐100) na protolitičke ravnoteže rupatadina.
Potenciometrijski su određene pKa vrednosti bez i u prisustvu 10‐2 M
surfaktanata, na temperaturi 25oC i pri konstantnoj jonskoj sili (0,1 M NaCl).
Potenciometrijski podaci analizirani su primenom programa Hyperquad. Nezavisno
određene pKa vrednosti fumarne kiseline korišćene su kao ulazni parametri za
određivanje pKa vrednosti rupatadina.
Određene su pKa vrednosti u vodenom rastvoru (pKa1=3,34; pKa2=4,72;
pKa3=6,75) i uočen je uticaj svih primenjenih surfaktanata, SDS (ΔpKa do +1,44); CTAB
(ΔpKa od ‐1,99 do +0,14); TX‐100 (ΔpKa od ‐0,72 do +0,38), na promenu jonizacije.
Jonizujući centri rupatadina uključuju se u elektrostatičke, hidrofobne, dipol interakcije
i vodonične veze sa micelama. Dijagram raspodele ravnotežnih oblika u funkciji pH
ukazuje da je promena raspodele najizraženija u pH oblasti 4 – 8 koja obuhvata
biofarmaceutski značajne pH vrednosti.
Pomeranje protolitičkih ravnoteža rupatadina pod uticajem micela ukazuje da
biomolekuli različite polarnosti i naelektrisanja u fiziološkim uslovima mogu izazvati
promenu raspodele ravnotežnih oblika od kojih zavise rastvorljivost i permeabilnost.
AB  - Rupatadine belongs to selective second‐generation histamine H1 receptors
antagonists, used in seasonal allergic rhinitis and chronic urticaria. Rupatadine contains
three ionizable basic centers, two aromatic and one cyclic aliphatic amine.
Pharmaceutical dosage forms contain rupatadine fumarate as an active substance.
Complex system of protolytic equilibria establishes in solution of rupatadine fumarate
including three rupatadine basic centers and two carboxylic groups of fumaric acid. The
pKa values are necessary for estimation of pharmacokinetic properties and
bioavailability of drugs. Under the physiological conditions protolytic equilibria could
be shifted due to interactions with biomolecules. The investigations of ionization in the
present of simplified biomembrane systems (micellar solutions of surfactants) give
better insight into physiological drug behavior. The effects of surfactants, sodium
dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and 4‐octylphenol
polyethoxylates (TX‐100) on rupatadine ionization have been investigated.
The pKa values were determined potentiometrically in the absence and in the
presence of 10‐2 M surfactants at 25°C and constant ionic strength (0.1 M NaCl).
Potentiometric data were analyzed in program Hyperquad. Independently determined
pKa values of fumaric acid were used as input parameters for determination of
rupatadine pKa values.
The ionization in water was defined (pKa1=3.34; pKa2=4.72; pKa3=6.75) and shift
in protolytic equilibria in the presence of micelles, SDS (ΔpKa up to +1.44); CTAB (ΔpKa
from ‐1.99 to +0.14); TX‐100 (ΔpKa from ‐0.72 to +0.38), were observed. The ionization
centers of rupatadine are involved in electrostatic, hydrophobic, dipole interactions,
and hydrogen bonds with micelles. Distribution diagram of equilibrium forms as a
function of pH indicates that change in ionization is the most expressed in pH range 4–8
which includes biopharmaceutically important pH values.
The shift in rupatadine protolytic equilibria indicates that biomolecules of
different charge and polarity could change distribution of equilibrium forms
responsible for solubility and permeability.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Uticaj micela različitog naelektrisanja kao simulirajućih sistema biomembrana na jonizaciju rupatadina
T1  - The effects of differently charged micelles as biomembrane mimetic systems on the ionization of rupatadine
VL  - 68
IS  - 3
SP  - 424
EP  - 425
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4879
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Stojilković, Kristina and Dobrosavljević, Maja",
year = "2018",
abstract = "Rupatadin je selektivni antagonist histaminskih H1 receptora druge generacije
koji se primenjuje u terapiji alergijskog rinitisa i hronične urtikarije. Rupatadin sadrži
tri jonizaciona centra, dva aromatična amina i jedan cikličan alkilamin. Dozirani
farmaceutski oblici za oralnu primenu kao aktivnu supstancu sadrže rupatadin fumarat.
U rastvoru rupatadin fumarata uspostavlja se složen sistem protolitičkih ravnoteža koji
uključuje tri bazna centra rupatadina i dve karboksilne grupe fumarne kiseline.
Poznavanje pKa vrednosti lekova neophodno je za procenu farmakokinetičkih osobina i
bioraspoloživosti. U fiziološkim uslovima pKa vrednosti mogu biti promenjene u odnosu
na vodeni rastvor usled interakcija sa naelektrisanim i polarnim biomolekulima.
Ispitivanje jonizacije u pojednostavljenim sistemima biomembrana, kao što su
micelarni rastvori surfaktanata, pruža bolji uvid u ponašanje lekova u fiziološkim
uslovima. Ispitan je uticaj micelarnih rastvora, anjonskog natrijum‐dodecilsulfata (SDS),
katjonskog cetiltrimetilamonijum‐bromida (CTAB) i nejonskog 4‐oktilfenol
polietoksilata (TX‐100) na protolitičke ravnoteže rupatadina.
Potenciometrijski su određene pKa vrednosti bez i u prisustvu 10‐2 M
surfaktanata, na temperaturi 25oC i pri konstantnoj jonskoj sili (0,1 M NaCl).
Potenciometrijski podaci analizirani su primenom programa Hyperquad. Nezavisno
određene pKa vrednosti fumarne kiseline korišćene su kao ulazni parametri za
određivanje pKa vrednosti rupatadina.
Određene su pKa vrednosti u vodenom rastvoru (pKa1=3,34; pKa2=4,72;
pKa3=6,75) i uočen je uticaj svih primenjenih surfaktanata, SDS (ΔpKa do +1,44); CTAB
(ΔpKa od ‐1,99 do +0,14); TX‐100 (ΔpKa od ‐0,72 do +0,38), na promenu jonizacije.
Jonizujući centri rupatadina uključuju se u elektrostatičke, hidrofobne, dipol interakcije
i vodonične veze sa micelama. Dijagram raspodele ravnotežnih oblika u funkciji pH
ukazuje da je promena raspodele najizraženija u pH oblasti 4 – 8 koja obuhvata
biofarmaceutski značajne pH vrednosti.
Pomeranje protolitičkih ravnoteža rupatadina pod uticajem micela ukazuje da
biomolekuli različite polarnosti i naelektrisanja u fiziološkim uslovima mogu izazvati
promenu raspodele ravnotežnih oblika od kojih zavise rastvorljivost i permeabilnost., Rupatadine belongs to selective second‐generation histamine H1 receptors
antagonists, used in seasonal allergic rhinitis and chronic urticaria. Rupatadine contains
three ionizable basic centers, two aromatic and one cyclic aliphatic amine.
Pharmaceutical dosage forms contain rupatadine fumarate as an active substance.
Complex system of protolytic equilibria establishes in solution of rupatadine fumarate
including three rupatadine basic centers and two carboxylic groups of fumaric acid. The
pKa values are necessary for estimation of pharmacokinetic properties and
bioavailability of drugs. Under the physiological conditions protolytic equilibria could
be shifted due to interactions with biomolecules. The investigations of ionization in the
present of simplified biomembrane systems (micellar solutions of surfactants) give
better insight into physiological drug behavior. The effects of surfactants, sodium
dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and 4‐octylphenol
polyethoxylates (TX‐100) on rupatadine ionization have been investigated.
The pKa values were determined potentiometrically in the absence and in the
presence of 10‐2 M surfactants at 25°C and constant ionic strength (0.1 M NaCl).
Potentiometric data were analyzed in program Hyperquad. Independently determined
pKa values of fumaric acid were used as input parameters for determination of
rupatadine pKa values.
The ionization in water was defined (pKa1=3.34; pKa2=4.72; pKa3=6.75) and shift
in protolytic equilibria in the presence of micelles, SDS (ΔpKa up to +1.44); CTAB (ΔpKa
from ‐1.99 to +0.14); TX‐100 (ΔpKa from ‐0.72 to +0.38), were observed. The ionization
centers of rupatadine are involved in electrostatic, hydrophobic, dipole interactions,
and hydrogen bonds with micelles. Distribution diagram of equilibrium forms as a
function of pH indicates that change in ionization is the most expressed in pH range 4–8
which includes biopharmaceutically important pH values.
The shift in rupatadine protolytic equilibria indicates that biomolecules of
different charge and polarity could change distribution of equilibrium forms
responsible for solubility and permeability.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Uticaj micela različitog naelektrisanja kao simulirajućih sistema biomembrana na jonizaciju rupatadina, The effects of differently charged micelles as biomembrane mimetic systems on the ionization of rupatadine",
volume = "68",
number = "3",
pages = "424-425",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4879"
}

Popović-Nikolić, M., Popović, G., Stojilković, K.,& Dobrosavljević, M.. (2018). Uticaj micela različitog naelektrisanja kao simulirajućih sistema biomembrana na jonizaciju rupatadina. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 68(3), 424-425.
https://hdl.handle.net/21.15107/rcub_farfar_4879

Popović-Nikolić M, Popović G, Stojilković K, Dobrosavljević M. Uticaj micela različitog naelektrisanja kao simulirajućih sistema biomembrana na jonizaciju rupatadina. in Arhiv za farmaciju. 2018;68(3):424-425.
https://hdl.handle.net/21.15107/rcub_farfar_4879 .

Popović-Nikolić, Marija, Popović, Gordana, Stojilković, Kristina, Dobrosavljević, Maja, "Uticaj micela različitog naelektrisanja kao simulirajućih sistema biomembrana na jonizaciju rupatadina" in Arhiv za farmaciju, 68, no. 3 (2018):424-425,
https://hdl.handle.net/21.15107/rcub_farfar_4879 .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Grujić, Maja
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3167
AB  - The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed. Energy calculation of the optimized structures of the equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of the theoretical study helped to assign the experimentally determined pK(a) values to the corresponding ionizable centers and confirmed that in all examined compounds, the higher pK(a) values can be attributed to ionization of tetrazole. The molecular descriptor values showed that sartans interact predominantly with the micelle surfaces. The equilibrium forms of ampholytes demonstrate higher affinity to the micelles, as compared to the forms of the diprotic acid. Additionally, it was shown that the uncharged molecular forms of ampholytes are more lipophylic then their zwitterionic forms.
PB  - Elsevier Science Inc, New York
T2  - Journal of Molecular Graphics & Modelling
T1  - A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles
VL  - 82
SP  - 67
EP  - 73
DO  - 10.1016/j.jmgm.2018.04.008
ER  - 

@article{
author = "Popović-Nikolić, Marija and Popović, Gordana and Grujić, Maja and Nikolić, Katarina and Agbaba, Danica",
year = "2018",
abstract = "The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed. Energy calculation of the optimized structures of the equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of the theoretical study helped to assign the experimentally determined pK(a) values to the corresponding ionizable centers and confirmed that in all examined compounds, the higher pK(a) values can be attributed to ionization of tetrazole. The molecular descriptor values showed that sartans interact predominantly with the micelle surfaces. The equilibrium forms of ampholytes demonstrate higher affinity to the micelles, as compared to the forms of the diprotic acid. Additionally, it was shown that the uncharged molecular forms of ampholytes are more lipophylic then their zwitterionic forms.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Molecular Graphics & Modelling",
title = "A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles",
volume = "82",
pages = "67-73",
doi = "10.1016/j.jmgm.2018.04.008"
}

Popović-Nikolić, M., Popović, G., Grujić, M., Nikolić, K.,& Agbaba, D.. (2018). A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles. in Journal of Molecular Graphics & Modelling
Elsevier Science Inc, New York., 82, 67-73.
https://doi.org/10.1016/j.jmgm.2018.04.008

Popović-Nikolić M, Popović G, Grujić M, Nikolić K, Agbaba D. A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles. in Journal of Molecular Graphics & Modelling. 2018;82:67-73.
doi:10.1016/j.jmgm.2018.04.008 .

Popović-Nikolić, Marija, Popović, Gordana, Grujić, Maja, Nikolić, Katarina, Agbaba, Danica, "A theoretical study on ionization of sartans in aqueous media and on interactions with surfactant micelles" in Journal of Molecular Graphics & Modelling, 82 (2018):67-73,
https://doi.org/10.1016/j.jmgm.2018.04.008 . .

TY  - JOUR
AU  - Ramsay, Rona R.
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Uliassi, Elisa
AU  - Bolognesi, Maria Laura
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3148
AB  - Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.
PB  - Springeropen, London
T2  - Clinical and Translational Medicine
T1  - A perspective on multi-target drug discovery and design for complex diseases
VL  - 7
DO  - 10.1186/s40169-017-0181-2
ER  - 

@article{
author = "Ramsay, Rona R. and Popović-Nikolić, Marija and Nikolić, Katarina and Uliassi, Elisa and Bolognesi, Maria Laura",
year = "2018",
abstract = "Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.",
publisher = "Springeropen, London",
journal = "Clinical and Translational Medicine",
title = "A perspective on multi-target drug discovery and design for complex diseases",
volume = "7",
doi = "10.1186/s40169-017-0181-2"
}

Ramsay, R. R., Popović-Nikolić, M., Nikolić, K., Uliassi, E.,& Bolognesi, M. L.. (2018). A perspective on multi-target drug discovery and design for complex diseases. in Clinical and Translational Medicine
Springeropen, London., 7.
https://doi.org/10.1186/s40169-017-0181-2

Ramsay RR, Popović-Nikolić M, Nikolić K, Uliassi E, Bolognesi ML. A perspective on multi-target drug discovery and design for complex diseases. in Clinical and Translational Medicine. 2018;7.
doi:10.1186/s40169-017-0181-2 .

Ramsay, Rona R., Popović-Nikolić, Marija, Nikolić, Katarina, Uliassi, Elisa, Bolognesi, Maria Laura, "A perspective on multi-target drug discovery and design for complex diseases" in Clinical and Translational Medicine, 7 (2018),
https://doi.org/10.1186/s40169-017-0181-2 . .

TY  - JOUR
AU  - Rupar, Jelena
AU  - Aleksić, Mara
AU  - Nikolić, Katarina
AU  - Popović-Nikolić, Marija
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3145
AB  - The electrochemical response of two biologically important benzopyrazine derivative, Quinoxaline and Brimonidine (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl) quinoxaline-6-amine) was studied at glassy carbon electrode. Investigations were performed in acetate buffer at pH 3.6 where both compounds undergo complex electrode process which begins with quasi reversible redox process at pyrazine ring forming di-hydro derivative, which is further irreversible oxidized to hydroxyl-derivative. Cyclic voltammetry at different scan rates was employed for the determination of heterogeneous electron transfer rate constant and diffusion coefficient of the compounds. The values of electron transfer rate constant at different temperatures were used for the evaluation of thermodynamic parameters like enthalpy, entropy and Gibbs free energy changes, as well as apparent energy of activation. Computational study has been performed in order to evaluate some useful quantum chemical parameters with the aim to confirm and explain the difference in experimentally obtained kinetic and thermodynamic parameters of the investigated QUI and BRIM redox process. Results were compared with studies of similar compounds and pointed out the observed similarities and differences.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Electrochimica Acta
T1  - Comparative electrochemical studies of kinetic and thermodynamic parameters of Quinoxaline and Brimonidine redox process
VL  - 271
SP  - 220
EP  - 231
DO  - 10.1016/j.electacta.2018.03.114
ER  - 

@article{
author = "Rupar, Jelena and Aleksić, Mara and Nikolić, Katarina and Popović-Nikolić, Marija",
year = "2018",
abstract = "The electrochemical response of two biologically important benzopyrazine derivative, Quinoxaline and Brimonidine (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl) quinoxaline-6-amine) was studied at glassy carbon electrode. Investigations were performed in acetate buffer at pH 3.6 where both compounds undergo complex electrode process which begins with quasi reversible redox process at pyrazine ring forming di-hydro derivative, which is further irreversible oxidized to hydroxyl-derivative. Cyclic voltammetry at different scan rates was employed for the determination of heterogeneous electron transfer rate constant and diffusion coefficient of the compounds. The values of electron transfer rate constant at different temperatures were used for the evaluation of thermodynamic parameters like enthalpy, entropy and Gibbs free energy changes, as well as apparent energy of activation. Computational study has been performed in order to evaluate some useful quantum chemical parameters with the aim to confirm and explain the difference in experimentally obtained kinetic and thermodynamic parameters of the investigated QUI and BRIM redox process. Results were compared with studies of similar compounds and pointed out the observed similarities and differences.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Electrochimica Acta",
title = "Comparative electrochemical studies of kinetic and thermodynamic parameters of Quinoxaline and Brimonidine redox process",
volume = "271",
pages = "220-231",
doi = "10.1016/j.electacta.2018.03.114"
}

Rupar, J., Aleksić, M., Nikolić, K.,& Popović-Nikolić, M.. (2018). Comparative electrochemical studies of kinetic and thermodynamic parameters of Quinoxaline and Brimonidine redox process. in Electrochimica Acta
Pergamon-Elsevier Science Ltd, Oxford., 271, 220-231.
https://doi.org/10.1016/j.electacta.2018.03.114

Rupar J, Aleksić M, Nikolić K, Popović-Nikolić M. Comparative electrochemical studies of kinetic and thermodynamic parameters of Quinoxaline and Brimonidine redox process. in Electrochimica Acta. 2018;271:220-231.
doi:10.1016/j.electacta.2018.03.114 .

Rupar, Jelena, Aleksić, Mara, Nikolić, Katarina, Popović-Nikolić, Marija, "Comparative electrochemical studies of kinetic and thermodynamic parameters of Quinoxaline and Brimonidine redox process" in Electrochimica Acta, 271 (2018):220-231,
https://doi.org/10.1016/j.electacta.2018.03.114 . .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Stojilković, Kristina
AU  - Dobrosavljević, Maja
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3065
AB  - The acid-base equilibria of rupatadine fumarate were investigated in the absence and the presence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate) surfactants. The pK(a) values of rupatadine and fumaric acid were potentiometrically determined at 25 degrees C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated with use of the computer program Hyperquad. Ionization in the surfactant-free media was defined, and the effects of surfactants on protolytic equilibria of rupatadine were estimated, based on a shift of the apparent ionization constants determined in micellar solutions against the pK(a) values in water. The anionic SDS micelles caused an increase in the pK(a) values of all the rupatadine ionization centers (Delta pK(a) up to +1.44), while the shift of protolytic equilibria in different directions was observed in the case of the cationic CTAB (Delta pK(a) from -1.99 to +0.14) and the nonionic TX -100 (Delta pK(a) from -0.72 to +0.38) micelles. Distribution diagrams of the equilibrium forms as a function of pH indicate that the change in distribution is most strongly expressed in the pH range 4-8 which includes biopharmaceutically important pH values.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Chemical and Engineering Data
T1  - Acid-Base Equilibria of Rupatadine Fumarate in Aqueous Media
VL  - 63
IS  - 8
SP  - 3150
EP  - 3156
DO  - 10.1021/acs.jced.8b00422
ER  - 

@article{
author = "Popović-Nikolić, Marija and Popović, Gordana and Stojilković, Kristina and Dobrosavljević, Maja and Agbaba, Danica",
year = "2018",
abstract = "The acid-base equilibria of rupatadine fumarate were investigated in the absence and the presence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate) surfactants. The pK(a) values of rupatadine and fumaric acid were potentiometrically determined at 25 degrees C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated with use of the computer program Hyperquad. Ionization in the surfactant-free media was defined, and the effects of surfactants on protolytic equilibria of rupatadine were estimated, based on a shift of the apparent ionization constants determined in micellar solutions against the pK(a) values in water. The anionic SDS micelles caused an increase in the pK(a) values of all the rupatadine ionization centers (Delta pK(a) up to +1.44), while the shift of protolytic equilibria in different directions was observed in the case of the cationic CTAB (Delta pK(a) from -1.99 to +0.14) and the nonionic TX -100 (Delta pK(a) from -0.72 to +0.38) micelles. Distribution diagrams of the equilibrium forms as a function of pH indicate that the change in distribution is most strongly expressed in the pH range 4-8 which includes biopharmaceutically important pH values.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Chemical and Engineering Data",
title = "Acid-Base Equilibria of Rupatadine Fumarate in Aqueous Media",
volume = "63",
number = "8",
pages = "3150-3156",
doi = "10.1021/acs.jced.8b00422"
}

Popović-Nikolić, M., Popović, G., Stojilković, K., Dobrosavljević, M.,& Agbaba, D.. (2018). Acid-Base Equilibria of Rupatadine Fumarate in Aqueous Media. in Journal of Chemical and Engineering Data
Amer Chemical Soc, Washington., 63(8), 3150-3156.
https://doi.org/10.1021/acs.jced.8b00422

Popović-Nikolić M, Popović G, Stojilković K, Dobrosavljević M, Agbaba D. Acid-Base Equilibria of Rupatadine Fumarate in Aqueous Media. in Journal of Chemical and Engineering Data. 2018;63(8):3150-3156.
doi:10.1021/acs.jced.8b00422 .

Popović-Nikolić, Marija, Popović, Gordana, Stojilković, Kristina, Dobrosavljević, Maja, Agbaba, Danica, "Acid-Base Equilibria of Rupatadine Fumarate in Aqueous Media" in Journal of Chemical and Engineering Data, 63, no. 8 (2018):3150-3156,
https://doi.org/10.1021/acs.jced.8b00422 . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4685
AB  - Rupatadine is selective second-generation H1 antagonist, used in seasonal allergic rhinitis
and chronic urticaria, and reported to be an antagonist to platelet-activating factor.
Rupatadine contains three ionizable basic centers, two aromatic and one cyclic aliphatic
amine. The pharmaceutical dosage forms for oral administration contain rupatadine
fumarate as an active substance. A complex system of protolytic equilibria establishes in
the solution of rupatadine fumarate which includes three basic centers of rupatadine and
two acidic groups of fumaric acid. The data on the physicochemical properties of drugs
determined in aqueous solution is not sufficient for the prediction of solubility and
bioavailability in physiological conditions that are significantly more complex. For a better
understanding of pharmacological behavior of ionizable drugs their physicochemical
properties should be investigated under conditions more similar to physiological. As the
biomembrane mimetic systems micellar solutions of surfactants can be used. The aim of
this study was to investigate the effect of micellar solutions of differently charged
surfactants sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and
4-octylphenol polyethoxylate (TX-100), as biomembrane mimetic systems, on protolytic
equilibria of rupatadine.
The solutions (5×10-4 M) with and without of the 0.01 M surfactants were titrated with
standard NaOH solution (0.0983 M) at a constant ionic strength (0.1 M NaCl) and
temperature 25°C. Experimental data obtained by potentiometric titration were analyzed
in the program Hyperquad.
The pKa values of rupatadine (pKa1 = 3.45, pKa2 = 4.72, pKa3 = 6.75) were determined and
the ionization was defined in aqueous media. The shift in protolytic equilibria was
observed based on the pKa values of rupatadine determined in the presence of
surfactants, anionic SDS (ΔpKa up to +1.44); cationic CTAB (ΔpKa up to -1.99) and nonionic
TX-100 (ΔpKa up to -0.69). Different types of interactions between rupatadine and micelles
were assumed.
Rupatadine ionizable groups participate in electrostatic interactions with the ionic SDS and
CTAB micelles and are involved in the interactions with a hydrophilic layer of nonionic
TX-100 micelles. Observed shift in protolytic equilibria at biopharmaceutically significante
pH values can be considered in the presence of biomolecules with various charge and
polarity in physiological conditions.
PB  - International Association of Physical Chemists
C3  - 6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK (Book of Abstracts)
T1  - Protolytic equilibria of rupatadine in micellar solutions of differently charged surfactants
SP  - 43
EP  - 43
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4685
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Agbaba, Danica",
year = "2017",
abstract = "Rupatadine is selective second-generation H1 antagonist, used in seasonal allergic rhinitis
and chronic urticaria, and reported to be an antagonist to platelet-activating factor.
Rupatadine contains three ionizable basic centers, two aromatic and one cyclic aliphatic
amine. The pharmaceutical dosage forms for oral administration contain rupatadine
fumarate as an active substance. A complex system of protolytic equilibria establishes in
the solution of rupatadine fumarate which includes three basic centers of rupatadine and
two acidic groups of fumaric acid. The data on the physicochemical properties of drugs
determined in aqueous solution is not sufficient for the prediction of solubility and
bioavailability in physiological conditions that are significantly more complex. For a better
understanding of pharmacological behavior of ionizable drugs their physicochemical
properties should be investigated under conditions more similar to physiological. As the
biomembrane mimetic systems micellar solutions of surfactants can be used. The aim of
this study was to investigate the effect of micellar solutions of differently charged
surfactants sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB) and
4-octylphenol polyethoxylate (TX-100), as biomembrane mimetic systems, on protolytic
equilibria of rupatadine.
The solutions (5×10-4 M) with and without of the 0.01 M surfactants were titrated with
standard NaOH solution (0.0983 M) at a constant ionic strength (0.1 M NaCl) and
temperature 25°C. Experimental data obtained by potentiometric titration were analyzed
in the program Hyperquad.
The pKa values of rupatadine (pKa1 = 3.45, pKa2 = 4.72, pKa3 = 6.75) were determined and
the ionization was defined in aqueous media. The shift in protolytic equilibria was
observed based on the pKa values of rupatadine determined in the presence of
surfactants, anionic SDS (ΔpKa up to +1.44); cationic CTAB (ΔpKa up to -1.99) and nonionic
TX-100 (ΔpKa up to -0.69). Different types of interactions between rupatadine and micelles
were assumed.
Rupatadine ionizable groups participate in electrostatic interactions with the ionic SDS and
CTAB micelles and are involved in the interactions with a hydrophilic layer of nonionic
TX-100 micelles. Observed shift in protolytic equilibria at biopharmaceutically significante
pH values can be considered in the presence of biomolecules with various charge and
polarity in physiological conditions.",
publisher = "International Association of Physical Chemists",
journal = "6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK (Book of Abstracts)",
title = "Protolytic equilibria of rupatadine in micellar solutions of differently charged surfactants",
pages = "43-43",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4685"
}

Popović-Nikolić, M., Popović, G.,& Agbaba, D.. (2017). Protolytic equilibria of rupatadine in micellar solutions of differently charged surfactants. in 6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK (Book of Abstracts)
International Association of Physical Chemists., 43-43.
https://hdl.handle.net/21.15107/rcub_farfar_4685

Popović-Nikolić M, Popović G, Agbaba D. Protolytic equilibria of rupatadine in micellar solutions of differently charged surfactants. in 6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK (Book of Abstracts). 2017;:43-43.
https://hdl.handle.net/21.15107/rcub_farfar_4685 .

Popović-Nikolić, Marija, Popović, Gordana, Agbaba, Danica, "Protolytic equilibria of rupatadine in micellar solutions of differently charged surfactants" in 6th IAPC Meeting Sixth World Conference on Physico-Chemical Methods in Drug Discovery & Third World Conference on ADMET and DMPK (Book of Abstracts) (2017):43-43,
https://hdl.handle.net/21.15107/rcub_farfar_4685 .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2899
AB  - Protolytic equilibria and solubility of verapamil were investigated in the presence and in the absence of nonionic surfactant Brij 35 at a constant ionic strength (0.1 mol/L NaCl) and temperature 25 degrees C. In surfactant free media the intrinsic solubility, S-o = 4.51 X 10(-5) mol/L (only the neutral form is present in the solution) and pH dependent solubility, S (neutral and ionized form in solution) of verapamil were determined. On the basis of the solubility data, the apparent pK(a) value 9.15 of verapamil was indirectly obtained. In micellar media (10(-3) mol/L Brij 35) the solubility of verapamil free base (S-0,S-s = 2.76 X 10(-3) mol/L) and the apparent pK(a,s) = 6.35, were determined. The shift in the protolytic equilibria (Delta pK(a) = -2.80) and the increased solubility of verapamil free base (approximately 60 times) caused by Brij 35 point out to specific interactions between verapamil and the inner part of Brij 35 micelles. The most significant changes in distribution of verapamil equilibrium forms were observed at biopharmaceutically important pH 7.4 which potentially indicates interactions with biomolecules in blood plasma.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Chemical and Engineering Data
T1  - The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil
VL  - 62
IS  - 6
SP  - 1776
EP  - 1781
DO  - 10.1021/acs.jced.6b00864
ER  - 

@article{
author = "Popović-Nikolić, Marija and Popović, Gordana and Agbaba, Danica",
year = "2017",
abstract = "Protolytic equilibria and solubility of verapamil were investigated in the presence and in the absence of nonionic surfactant Brij 35 at a constant ionic strength (0.1 mol/L NaCl) and temperature 25 degrees C. In surfactant free media the intrinsic solubility, S-o = 4.51 X 10(-5) mol/L (only the neutral form is present in the solution) and pH dependent solubility, S (neutral and ionized form in solution) of verapamil were determined. On the basis of the solubility data, the apparent pK(a) value 9.15 of verapamil was indirectly obtained. In micellar media (10(-3) mol/L Brij 35) the solubility of verapamil free base (S-0,S-s = 2.76 X 10(-3) mol/L) and the apparent pK(a,s) = 6.35, were determined. The shift in the protolytic equilibria (Delta pK(a) = -2.80) and the increased solubility of verapamil free base (approximately 60 times) caused by Brij 35 point out to specific interactions between verapamil and the inner part of Brij 35 micelles. The most significant changes in distribution of verapamil equilibrium forms were observed at biopharmaceutically important pH 7.4 which potentially indicates interactions with biomolecules in blood plasma.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Chemical and Engineering Data",
title = "The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil",
volume = "62",
number = "6",
pages = "1776-1781",
doi = "10.1021/acs.jced.6b00864"
}

Popović-Nikolić, M., Popović, G.,& Agbaba, D.. (2017). The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil. in Journal of Chemical and Engineering Data
Amer Chemical Soc, Washington., 62(6), 1776-1781.
https://doi.org/10.1021/acs.jced.6b00864

Popović-Nikolić M, Popović G, Agbaba D. The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil. in Journal of Chemical and Engineering Data. 2017;62(6):1776-1781.
doi:10.1021/acs.jced.6b00864 .

Popović-Nikolić, Marija, Popović, Gordana, Agbaba, Danica, "The Effect of Nonionic Surfactant Brij 35 on Solubility and Acid-Base Equilibria of Verapamil" in Journal of Chemical and Engineering Data, 62, no. 6 (2017):1776-1781,
https://doi.org/10.1021/acs.jced.6b00864 . .

TY  - JOUR
AU  - Vučićević, Jelica
AU  - Popović, Marija
AU  - Nikolić, Katarina
AU  - Filipić, Slavica
AU  - Obradović, Darija
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2900
AB  - For this study, 31 compounds, including 16 imidazoline/alpha-adrenergic receptor (IRs/alpha-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k (BMC) and log k (wRP), respectively). Based on the retention factor (log k(wRP)) and slope of the linear curve (S) the isocratic parameter ((sic)(0)) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k(BMC) /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k(wRP) /log BB): 0.58; r(S/log BB): -0.50; r((sic)(0) /P-e): 0.61). Based on the log k(BMC) retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/alpha-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Saudi Pharmaceutical Journal
T1  - Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis
VL  - 28
IS  - 3
SP  - 235
EP  - 252
DO  - 10.1080/1062936X.2017.1302506
ER  - 

@article{
author = "Vučićević, Jelica and Popović, Marija and Nikolić, Katarina and Filipić, Slavica and Obradović, Darija and Agbaba, Danica",
year = "2017",
abstract = "For this study, 31 compounds, including 16 imidazoline/alpha-adrenergic receptor (IRs/alpha-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k (BMC) and log k (wRP), respectively). Based on the retention factor (log k(wRP)) and slope of the linear curve (S) the isocratic parameter ((sic)(0)) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k(BMC) /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k(wRP) /log BB): 0.58; r(S/log BB): -0.50; r((sic)(0) /P-e): 0.61). Based on the log k(BMC) retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/alpha-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Saudi Pharmaceutical Journal",
title = "Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis",
volume = "28",
number = "3",
pages = "235-252",
doi = "10.1080/1062936X.2017.1302506"
}

Vučićević, J., Popović, M., Nikolić, K., Filipić, S., Obradović, D.,& Agbaba, D.. (2017). Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis. in Saudi Pharmaceutical Journal
Taylor & Francis Ltd, Abingdon., 28(3), 235-252.
https://doi.org/10.1080/1062936X.2017.1302506

Vučićević J, Popović M, Nikolić K, Filipić S, Obradović D, Agbaba D. Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis. in Saudi Pharmaceutical Journal. 2017;28(3):235-252.
doi:10.1080/1062936X.2017.1302506 .

Vučićević, Jelica, Popović, Marija, Nikolić, Katarina, Filipić, Slavica, Obradović, Darija, Agbaba, Danica, "Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of alpha-adrenergic/imidazoline receptor ligands, and QSPR analysis" in Saudi Pharmaceutical Journal, 28, no. 3 (2017):235-252,
https://doi.org/10.1080/1062936X.2017.1302506 . .

TY  - CONF
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Popović, Marija
AU  - Filipić, Slavica
AU  - Obradović, Darija
AU  - Dobričić, Vladimir
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5027
AB  - Imidazoline receptor ligands are a numerous
family of biologically active compounds
known to produce central hypotensive effect
by interaction with both alpha2-adrenoreceptors
(alpha2-AR) and imidazoline receptors (IRs) (1,
2).
The main aims of this study were to evaluate
Blood-Brain Barrier (BBB) permeability (Pe)
of 18 IRs/alpha-ARs ligands and 22 Central
Nervous System (CNS) drugs using Parallel
Artificial Membrane Permeability Assay
(PAMPA) and Biopartitioning Micellar
Chromatography (BMC), and than to develop
the Quantitative-Structure-Permeability
Relationship (QSPR) models useful for
prediction BBB permeability of related IRs/alpha-
ARs ligands.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia
T1  - Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling
VL  - 66
SP  - 25
EP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5027
ER  - 

@conference{
author = "Nikolić, Katarina and Vučićević, Jelica and Popović, Marija and Filipić, Slavica and Obradović, Darija and Dobričić, Vladimir and Agbaba, Danica",
year = "2016",
abstract = "Imidazoline receptor ligands are a numerous
family of biologically active compounds
known to produce central hypotensive effect
by interaction with both alpha2-adrenoreceptors
(alpha2-AR) and imidazoline receptors (IRs) (1,
2).
The main aims of this study were to evaluate
Blood-Brain Barrier (BBB) permeability (Pe)
of 18 IRs/alpha-ARs ligands and 22 Central
Nervous System (CNS) drugs using Parallel
Artificial Membrane Permeability Assay
(PAMPA) and Biopartitioning Micellar
Chromatography (BMC), and than to develop
the Quantitative-Structure-Permeability
Relationship (QSPR) models useful for
prediction BBB permeability of related IRs/alpha-
ARs ligands.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia",
title = "Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling",
volume = "66",
pages = "25-26",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5027"
}

Nikolić, K., Vučićević, J., Popović, M., Filipić, S., Obradović, D., Dobričić, V.,& Agbaba, D.. (2016). Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling. in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia
Savez farmaceutskih udruženja Srbije, Beograd., 66, 25-26.
https://hdl.handle.net/21.15107/rcub_farfar_5027

Nikolić K, Vučićević J, Popović M, Filipić S, Obradović D, Dobričić V, Agbaba D. Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling. in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia. 2016;66:25-26.
https://hdl.handle.net/21.15107/rcub_farfar_5027 .

Nikolić, Katarina, Vučićević, Jelica, Popović, Marija, Filipić, Slavica, Obradović, Darija, Dobričić, Vladimir, Agbaba, Danica, "Study of bloodbrain barrier permeation using parallel artificial membrane permeability assay and quantitative structure permeability relationship modeling" in Arhiv za farmaciju, Special Issue, Book of Abstracts, 11 Central European Symposium on Pharmaceutical Technology, September 22 – 24, 2016 Belgrade, Serbia, 66 (2016):25-26,
https://hdl.handle.net/21.15107/rcub_farfar_5027 .