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  - 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  - 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  - 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  - Dimitrijević, Marija
AU  - Mitić, Violeta
AU  - Đorđević, Dragan
AU  - Popović, Gordana
AU  - Krstić, Nenad
AU  - Nikolić, Jelena
AU  - Stankov Jovanović, Vesna
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3988
AB  - Three edible mushrooms of the Russulacea family (Lactarius deliciosus, Lactarius sanguifluus and Lactarius semisanguifluus), most frequently consumed in Serbia, were analyzed using the ICP-OES technique to evaluate the content of K, P, Ca, Mg, Na, Al, As, Cd and Pb, both in cap and stipe. Corresponding soils were analyzed, too. Based on the obtained values for the elemental composition of the mushrooms and the soil, bioaccumulation and translocation factors were calculated. All the examined mushrooms species were recognized as bioexclusors of analyzed toxic elements, but bioaccumulators of K, P and Ca. The studied mushrooms are good sources of macroelements. One portion of 300 g of fresh mushrooms had a significant contribution of K and P, exceeding 15 % of the recommended daily intake for the elements. On the contrary, mushrooms had a low potential to bioaccumulate toxic elements, and presented results indicated the regular consumption of wild edible mushrooms is safe for human health. Correlation analysis was applied to determine phosphorus’s influence on the elements’ content in the mushrooms and corresponding soils, demonstrating the most remarkable mushrooms' tendency to accumulate phosphorus.
AB  - Циљ овог рада било је одређивање садржаја K, P, Ca, Mg, Na, Al, As, Cd и Pb у три
јестиве, самоникле печурке (Lactarius deliciosus, Lactarius sanguifluus и Lactarius semisanguifluus)
које припадају породици Russulacea. Такође, одређен је и садржај поменутих
елемената у земљишту на коме су расле анализиране печурке. На основу добијених
резултата, за сваки елемент је израчунат биоакумулациони и транслокациони фактор.
Будући да је утврђено да печурке акумулирају одговарајуће макроелементе, резултати
су приказани и као унос (%) одговарајућих елемената на основу препоручене дневне
дозе, прерачунато на порцију од 300 g свежих печурака. За токсичне елементе израчунат
је садржај уноса елемената на основу прихватљивог недељног уноса. Корелациона ана-
лиза је коришћена како би се утврдио утицај фосфора на садржај елемената у печур-
кама и одговарајућим земљиштима, обзиром да је фосфор показао најзначајнију тен-
денцију акумулације.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Macroelements versus toxic elements in selected wild edible mushrooms of the Russulacea family from Serbia
VL  - 86
IS  - 10
SP  - 927
EP  - 940
DO  - 10.2298/JSC210410038D
ER  - 

@article{
author = "Dimitrijević, Marija and Mitić, Violeta and Đorđević, Dragan and Popović, Gordana and Krstić, Nenad and Nikolić, Jelena and Stankov Jovanović, Vesna",
year = "2021",
abstract = "Three edible mushrooms of the Russulacea family (Lactarius deliciosus, Lactarius sanguifluus and Lactarius semisanguifluus), most frequently consumed in Serbia, were analyzed using the ICP-OES technique to evaluate the content of K, P, Ca, Mg, Na, Al, As, Cd and Pb, both in cap and stipe. Corresponding soils were analyzed, too. Based on the obtained values for the elemental composition of the mushrooms and the soil, bioaccumulation and translocation factors were calculated. All the examined mushrooms species were recognized as bioexclusors of analyzed toxic elements, but bioaccumulators of K, P and Ca. The studied mushrooms are good sources of macroelements. One portion of 300 g of fresh mushrooms had a significant contribution of K and P, exceeding 15 % of the recommended daily intake for the elements. On the contrary, mushrooms had a low potential to bioaccumulate toxic elements, and presented results indicated the regular consumption of wild edible mushrooms is safe for human health. Correlation analysis was applied to determine phosphorus’s influence on the elements’ content in the mushrooms and corresponding soils, demonstrating the most remarkable mushrooms' tendency to accumulate phosphorus., Циљ овог рада било је одређивање садржаја K, P, Ca, Mg, Na, Al, As, Cd и Pb у три
јестиве, самоникле печурке (Lactarius deliciosus, Lactarius sanguifluus и Lactarius semisanguifluus)
које припадају породици Russulacea. Такође, одређен је и садржај поменутих
елемената у земљишту на коме су расле анализиране печурке. На основу добијених
резултата, за сваки елемент је израчунат биоакумулациони и транслокациони фактор.
Будући да је утврђено да печурке акумулирају одговарајуће макроелементе, резултати
су приказани и као унос (%) одговарајућих елемената на основу препоручене дневне
дозе, прерачунато на порцију од 300 g свежих печурака. За токсичне елементе израчунат
је садржај уноса елемената на основу прихватљивог недељног уноса. Корелациона ана-
лиза је коришћена како би се утврдио утицај фосфора на садржај елемената у печур-
кама и одговарајућим земљиштима, обзиром да је фосфор показао најзначајнију тен-
денцију акумулације.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Macroelements versus toxic elements in selected wild edible mushrooms of the Russulacea family from Serbia",
volume = "86",
number = "10",
pages = "927-940",
doi = "10.2298/JSC210410038D"
}

Dimitrijević, M., Mitić, V., Đorđević, D., Popović, G., Krstić, N., Nikolić, J.,& Stankov Jovanović, V.. (2021). Macroelements versus toxic elements in selected wild edible mushrooms of the Russulacea family from Serbia. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 86(10), 927-940.
https://doi.org/10.2298/JSC210410038D

Dimitrijević M, Mitić V, Đorđević D, Popović G, Krstić N, Nikolić J, Stankov Jovanović V. Macroelements versus toxic elements in selected wild edible mushrooms of the Russulacea family from Serbia. in Journal of the Serbian Chemical Society. 2021;86(10):927-940.
doi:10.2298/JSC210410038D .

Dimitrijević, Marija, Mitić, Violeta, Đorđević, Dragan, Popović, Gordana, Krstić, Nenad, Nikolić, Jelena, Stankov Jovanović, Vesna, "Macroelements versus toxic elements in selected wild edible mushrooms of the Russulacea family from Serbia" in Journal of the Serbian Chemical Society, 86, no. 10 (2021):927-940,
https://doi.org/10.2298/JSC210410038D . .

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  - 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  - CONF
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Nikolić, Katarina
AU  - Grujić, Maja
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5026
AB  - In this study the order of ionization in the molecules of irbesartan, losartan,
and valsartan has been investigated. Irbesartan and losartan are ampholytes,
valsartan is diacid with close values of ionization constants. In order to get
better insight in the overlapped protolytic equilibria of sartans theoretical
study was performed. Energy calculation of the optimized structures of
equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the
Density Functional Theory (DFT). Results of theoretical study
confirmed prediction that in all examined compounds higher pKa values can be
attributed to the ionization of tetrazole.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - Theoretical study of ionization of sartansin aqueous media
VL  - II
SP  - 801
EP  - 804
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5026
ER  - 

@conference{
author = "Popović, Marija and Popović, Gordana and Nikolić, Katarina and Grujić, Maja and Agbaba, Danica",
year = "2016",
abstract = "In this study the order of ionization in the molecules of irbesartan, losartan,
and valsartan has been investigated. Irbesartan and losartan are ampholytes,
valsartan is diacid with close values of ionization constants. In order to get
better insight in the overlapped protolytic equilibria of sartans theoretical
study was performed. Energy calculation of the optimized structures of
equilibrium forms was performed at the B3LYP/6-31G (d,p) level of the
Density Functional Theory (DFT). Results of theoretical study
confirmed prediction that in all examined compounds higher pKa values can be
attributed to the ionization of tetrazole.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "Theoretical study of ionization of sartansin aqueous media",
volume = "II",
pages = "801-804",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5026"
}

Popović, M., Popović, G., Nikolić, K., Grujić, M.,& Agbaba, D.. (2016). Theoretical study of ionization of sartansin aqueous media. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 801-804.
https://hdl.handle.net/21.15107/rcub_farfar_5026

Popović M, Popović G, Nikolić K, Grujić M, Agbaba D. Theoretical study of ionization of sartansin aqueous media. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:801-804.
https://hdl.handle.net/21.15107/rcub_farfar_5026 .

Popović, Marija, Popović, Gordana, Nikolić, Katarina, Grujić, Maja, Agbaba, Danica, "Theoretical study of ionization of sartansin aqueous media" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):801-804,
https://hdl.handle.net/21.15107/rcub_farfar_5026 .

TY  - CONF
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Stojadinović, Milica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5024
AB  - The intrinsic solubility – S0 (only the neutral form is present in the solution)
and pH-dependent solubility - S (heterogeneous system of neutral and
ionized forms) of verapamil were determined spectrophotometrically. Based
on solubility data pKa value 9.15 of verapamil was indirectly obtained.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - Acid-base equilibria and solubility of verapamil
VL  - II
SP  - 797
EP  - 800
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5024
ER  - 

@conference{
author = "Popović, Marija and Popović, Gordana and Stojadinović, Milica",
year = "2016",
abstract = "The intrinsic solubility – S0 (only the neutral form is present in the solution)
and pH-dependent solubility - S (heterogeneous system of neutral and
ionized forms) of verapamil were determined spectrophotometrically. Based
on solubility data pKa value 9.15 of verapamil was indirectly obtained.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "Acid-base equilibria and solubility of verapamil",
volume = "II",
pages = "797-800",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5024"
}

Popović, M., Popović, G.,& Stojadinović, M.. (2016). Acid-base equilibria and solubility of verapamil. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 797-800.
https://hdl.handle.net/21.15107/rcub_farfar_5024

Popović M, Popović G, Stojadinović M. Acid-base equilibria and solubility of verapamil. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:797-800.
https://hdl.handle.net/21.15107/rcub_farfar_5024 .

Popović, Marija, Popović, Gordana, Stojadinović, Milica, "Acid-base equilibria and solubility of verapamil" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):797-800,
https://hdl.handle.net/21.15107/rcub_farfar_5024 .

TY  - CONF
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Škrijelj, Edina
AU  - Tomić, A
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5023
AB  - The intrinsic solubility – S0 (only the neutral form is present in the solution)
of verapamil were investigated in the presence of nonionic micelles (Brij 35
and TX-100) and in surfactant free media. Brij 35 micelles caused the
increase in verapamil solubility. The phase separation was observed in
solution of TX-100 in the presence of verapamil which points out to specific
interactions between verapamil and this surfactant.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
T1  - The effect of nonionic surfactants on verapamil solubility
VL  - II
SP  - 805
EP  - 808
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5023
ER  - 

@conference{
author = "Popović, Marija and Popović, Gordana and Škrijelj, Edina and Tomić, A",
year = "2016",
abstract = "The intrinsic solubility – S0 (only the neutral form is present in the solution)
of verapamil were investigated in the presence of nonionic micelles (Brij 35
and TX-100) and in surfactant free media. Brij 35 micelles caused the
increase in verapamil solubility. The phase separation was observed in
solution of TX-100 in the presence of verapamil which points out to specific
interactions between verapamil and this surfactant.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia",
title = "The effect of nonionic surfactants on verapamil solubility",
volume = "II",
pages = "805-808",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5023"
}

Popović, M., Popović, G., Škrijelj, E.,& Tomić, A.. (2016). The effect of nonionic surfactants on verapamil solubility. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia
Society of Physical Chemists of Serbia., II, 805-808.
https://hdl.handle.net/21.15107/rcub_farfar_5023

Popović M, Popović G, Škrijelj E, Tomić A. The effect of nonionic surfactants on verapamil solubility. in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia. 2016;II:805-808.
https://hdl.handle.net/21.15107/rcub_farfar_5023 .

Popović, Marija, Popović, Gordana, Škrijelj, Edina, Tomić, A, "The effect of nonionic surfactants on verapamil solubility" in PHYSICAL CHEMISTRY 2016 (Proceedings) 13th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 26-30, 2016, Belgrade, Serbia, II (2016):805-808,
https://hdl.handle.net/21.15107/rcub_farfar_5023 .

TY  - JOUR
AU  - Grujić, Maja
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2715
AB  - Protolytic equilibria of irbesartan, losartan, and valsartan have been investigated in the presence and absence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate and polyoxyethylene (23) lauryl ether) surfactants. Ionization constants were determined by potentiometric titration at a constant ionic strength (0.1 M NaCl) and temperature 25 degrees C. The effect of surfactants was estimated, based on a shift in apparent ionization constants (pK(a)(app)) determined in micellar solutions against the pK(a)(w) values in water. The anionic surfactant caused an increase in the pK(a)(app) values of sartans (up to 1.72 pK units), while the cationic surfactant had an opposite effect and caused a reduction in pK(a)(app) values (up to -1.44 pK units). These results point out to the fact that the ionizable groups of sartans are involved in electrostatic interactions with the charged surface of the ionic micelles. Shift in the pKa app values in the presence of nonionic surfactants (from -0.86 to +1.30) is a consequence of the interactions of drugs with the hydrophilic palisade layer. Significant changes in the distribution profiles of the equilibrium forms (from -44% to +80%) are observed at the biopharmaceutically important pH 4.5 value and can be considered in terms of the potential influence on intestinal absorption and bioavailability.
PB  - Wiley, Hoboken
T2  - Journal of Pharmaceutical Sciences
T1  - Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants
VL  - 105
IS  - 8
SP  - 2444
EP  - 2452
DO  - 10.1016/j.xphs.2016.06.007
ER  - 

@article{
author = "Grujić, Maja and Popović, Marija and Popović, Gordana and Nikolić, Katarina and Agbaba, Danica",
year = "2016",
abstract = "Protolytic equilibria of irbesartan, losartan, and valsartan have been investigated in the presence and absence of differently charged anionic (sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and nonionic (4-octylphenol polyethoxylate and polyoxyethylene (23) lauryl ether) surfactants. Ionization constants were determined by potentiometric titration at a constant ionic strength (0.1 M NaCl) and temperature 25 degrees C. The effect of surfactants was estimated, based on a shift in apparent ionization constants (pK(a)(app)) determined in micellar solutions against the pK(a)(w) values in water. The anionic surfactant caused an increase in the pK(a)(app) values of sartans (up to 1.72 pK units), while the cationic surfactant had an opposite effect and caused a reduction in pK(a)(app) values (up to -1.44 pK units). These results point out to the fact that the ionizable groups of sartans are involved in electrostatic interactions with the charged surface of the ionic micelles. Shift in the pKa app values in the presence of nonionic surfactants (from -0.86 to +1.30) is a consequence of the interactions of drugs with the hydrophilic palisade layer. Significant changes in the distribution profiles of the equilibrium forms (from -44% to +80%) are observed at the biopharmaceutically important pH 4.5 value and can be considered in terms of the potential influence on intestinal absorption and bioavailability.",
publisher = "Wiley, Hoboken",
journal = "Journal of Pharmaceutical Sciences",
title = "Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants",
volume = "105",
number = "8",
pages = "2444-2452",
doi = "10.1016/j.xphs.2016.06.007"
}

Grujić, M., Popović, M., Popović, G., Nikolić, K.,& Agbaba, D.. (2016). Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants. in Journal of Pharmaceutical Sciences
Wiley, Hoboken., 105(8), 2444-2452.
https://doi.org/10.1016/j.xphs.2016.06.007

Grujić M, Popović M, Popović G, Nikolić K, Agbaba D. Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants. in Journal of Pharmaceutical Sciences. 2016;105(8):2444-2452.
doi:10.1016/j.xphs.2016.06.007 .

Grujić, Maja, Popović, Marija, Popović, Gordana, Nikolić, Katarina, Agbaba, Danica, "Protolytic Equilibria of Sartans in Micellar Solutions of Differently Charged Surfactants" in Journal of Pharmaceutical Sciences, 105, no. 8 (2016):2444-2452,
https://doi.org/10.1016/j.xphs.2016.06.007 . .

TY  - CONF
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Filipić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5046
AB  - Enalapril and ramipril are structuraly very similar compounds which belong to the class of angiotensin-converting enzyme (ACE) inhibitors and can be classified as proline peptide bond-containing dipeptides. Because of a resonance stabilization and partially double bond character, these compounds can exist in both (Z)- and (E)-diastereomers. ...
PB  - National Institute of Chemistry, Slovenia
C3  - 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS
T1  - RP-HPLC and DFT study on separation of enalapril and ramipril (Z)- and (E)-diastereomers
SP  - 67
EP  - 67
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5046
ER  - 

@conference{
author = "Popović, Marija and Popović, Gordana and Filipić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2015",
abstract = "Enalapril and ramipril are structuraly very similar compounds which belong to the class of angiotensin-converting enzyme (ACE) inhibitors and can be classified as proline peptide bond-containing dipeptides. Because of a resonance stabilization and partially double bond character, these compounds can exist in both (Z)- and (E)-diastereomers. ...",
publisher = "National Institute of Chemistry, Slovenia",
journal = "21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS",
title = "RP-HPLC and DFT study on separation of enalapril and ramipril (Z)- and (E)-diastereomers",
pages = "67-67",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5046"
}

Popović, M., Popović, G., Filipić, S., Nikolić, K.,& Agbaba, D.. (2015). RP-HPLC and DFT study on separation of enalapril and ramipril (Z)- and (E)-diastereomers. in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS
National Institute of Chemistry, Slovenia., 67-67.
https://hdl.handle.net/21.15107/rcub_farfar_5046

Popović M, Popović G, Filipić S, Nikolić K, Agbaba D. RP-HPLC and DFT study on separation of enalapril and ramipril (Z)- and (E)-diastereomers. in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS. 2015;:67-67.
https://hdl.handle.net/21.15107/rcub_farfar_5046 .

Popović, Marija, Popović, Gordana, Filipić, Slavica, Nikolić, Katarina, Agbaba, Danica, "RP-HPLC and DFT study on separation of enalapril and ramipril (Z)- and (E)-diastereomers" in 21st International Symposium on Separation Sciences, BOOK OF ABSTRACTS (2015):67-67,
https://hdl.handle.net/21.15107/rcub_farfar_5046 .

TY  - JOUR
AU  - Popović, Marija
AU  - Popović, Gordana
AU  - Filipić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2394
AB  - The (Z)/(E) equilibria in water solutions of five ACE inhibitors (captopril, enalapril, lisinopril, perindopril, and ramipril) in presence and in absence of surfactants (anionic sodium dodecyl sulfate, cationic cetyltrimethyl ammonium bromide, and non-ionic 4-octylphenol polyethoxylate) were analyzed by reversed-phase high-performance liquid chromatography. The results showed that the (Z)/(E) equilibrium of lisinopril and captopril was the least sensitive to the effect of the examined surfactants. 4-Octylphenol polyethoxylate expressed the weakest effect on isomerization of the ACE inhibitors, while the (Z)/(E) equilibria of enalapril, ramipril, and perindopril were the most sensitive to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide. In addition, the response of two structurally very close compounds, such as enalapril and ramipril to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide was opposite, and these two ACE inhibitors had different chromatographic behavior. To provide a better insight into the reasons for the differences in order of elution of (Z)- and (E)-diastereomers and the possible molecular mechanism underlying their retention, (Z)- and (E)-diastereomers of enalapril and ramipril were subjected to a theoretical study optimized at the B3LYP/6-31G (d,p) level of density functional theory. The Connolly solvent-excluded volume was taken as the most significant parameter that can be connected to differences in chromatographic behavior of the (Z)- and (E)-diastereomers of enalapril and ramipril. [GRAPHICS]
PB  - Springer Wien, Wien
T2  - Monatshefte für Chemie Chemical Monthly
T1  - The effects of micelles of differently charged surfactants on the equilibrium between (Z)- and (E)-diastereomers of five ACE inhibitors in aqueous media
VL  - 146
IS  - 6
SP  - 913
EP  - 921
DO  - 10.1007/s00706-014-1400-9
ER  - 

@article{
author = "Popović, Marija and Popović, Gordana and Filipić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2015",
abstract = "The (Z)/(E) equilibria in water solutions of five ACE inhibitors (captopril, enalapril, lisinopril, perindopril, and ramipril) in presence and in absence of surfactants (anionic sodium dodecyl sulfate, cationic cetyltrimethyl ammonium bromide, and non-ionic 4-octylphenol polyethoxylate) were analyzed by reversed-phase high-performance liquid chromatography. The results showed that the (Z)/(E) equilibrium of lisinopril and captopril was the least sensitive to the effect of the examined surfactants. 4-Octylphenol polyethoxylate expressed the weakest effect on isomerization of the ACE inhibitors, while the (Z)/(E) equilibria of enalapril, ramipril, and perindopril were the most sensitive to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide. In addition, the response of two structurally very close compounds, such as enalapril and ramipril to the presence of sodium dodecyl sulfate and cetyltrimethyl ammonium bromide was opposite, and these two ACE inhibitors had different chromatographic behavior. To provide a better insight into the reasons for the differences in order of elution of (Z)- and (E)-diastereomers and the possible molecular mechanism underlying their retention, (Z)- and (E)-diastereomers of enalapril and ramipril were subjected to a theoretical study optimized at the B3LYP/6-31G (d,p) level of density functional theory. The Connolly solvent-excluded volume was taken as the most significant parameter that can be connected to differences in chromatographic behavior of the (Z)- and (E)-diastereomers of enalapril and ramipril. [GRAPHICS]",
publisher = "Springer Wien, Wien",
journal = "Monatshefte für Chemie Chemical Monthly",
title = "The effects of micelles of differently charged surfactants on the equilibrium between (Z)- and (E)-diastereomers of five ACE inhibitors in aqueous media",
volume = "146",
number = "6",
pages = "913-921",
doi = "10.1007/s00706-014-1400-9"
}

Popović, M., Popović, G., Filipić, S., Nikolić, K.,& Agbaba, D.. (2015). The effects of micelles of differently charged surfactants on the equilibrium between (Z)- and (E)-diastereomers of five ACE inhibitors in aqueous media. in Monatshefte für Chemie Chemical Monthly
Springer Wien, Wien., 146(6), 913-921.
https://doi.org/10.1007/s00706-014-1400-9

Popović M, Popović G, Filipić S, Nikolić K, Agbaba D. The effects of micelles of differently charged surfactants on the equilibrium between (Z)- and (E)-diastereomers of five ACE inhibitors in aqueous media. in Monatshefte für Chemie Chemical Monthly. 2015;146(6):913-921.
doi:10.1007/s00706-014-1400-9 .

Popović, Marija, Popović, Gordana, Filipić, Slavica, Nikolić, Katarina, Agbaba, Danica, "The effects of micelles of differently charged surfactants on the equilibrium between (Z)- and (E)-diastereomers of five ACE inhibitors in aqueous media" in Monatshefte für Chemie Chemical Monthly, 146, no. 6 (2015):913-921,
https://doi.org/10.1007/s00706-014-1400-9 . .

TY  - CONF
AU  - Filipić, Slavica
AU  - Nikolić, Katarina
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5201
AB  - Guanidine and imidazoline derivatives belong to the family of imidazoline receptors ligands with diverse pharmacological effects on cardiovascular system. The presence of guanidine and imidazoline moieties gives them the properties of bases. Knowledge of their acidity constants (pKa values) and degree of ionization are important not only for analyitical procedures but also for their pharmacokinetic properties and activity. The main objective of this work was to determine the pKa values of 10 guanidine and imidazoline derivatives: moxonidine, clonidine, rilmenidine, tizanidine, idazoxan, efaroxan, guanfacine, harmane, harmine, and triamterene by capillary electrophoresis. The effective electrophoretic mobilities were measured by capillary zone electrophoresis in series of background electrolytes with broad pH range (4.00-11.00), with constant ionic strength (25 mM) and temperature (25 °C). All experiments were performed using an uncoated fused capillary (31.5 cm × 50 mm id). The samples were injected hydrodynamically at 11 kV and monitored at 200 nm. Acetone was used as marker of electroosmotic flow. The pKa values were determined by nonlinear regression analysis of the experimentally measured pH dependence of their effective electrophoretic mobilities. Thermodynamic pKa values of analysed compounds were estimated to be in the range from 6.21 for triamterene to 9.45 for efaroxan. Among 2-aminoimidazoline derivatives the strongest basic character posses clonidine with pKa 8.02 while moxonidine (pKa 7.35) and tizanidine (pKa 7.36) have slightly lower and very close pKa values. 
According to the obtained results and compared to the literature data capillary electrophoresis can be used as fast, simple and reliable method for determination of pKa values of related compounds.
AB  - Derivati gvanidina i imidazolina pripadaju grupi liganada imidazolinskih receptora sa različitim farmakološkim efektima na kardiovaskularni sistem. Prisustvo gvanidina i imizolina u njihovoj strukturi daje im bazni karakter. Poznavanje kiselinskih konstanti (pKa vrednosti) i stepena jonizacije ove grupe jednjenja značajno je kako sa analitičkog aspekta, tako is a aspekta njihovih farmakokinetičkih osobina i dejstva. Cilj ovog rada bio je da se odrede pKa vrednosti 10 derivata gvanidina i imidazolina: moksonidina, klonidina, rilmenidina, tizanidina, idazoksana, efaroksana, gvanfacina, harmana, harmina i triamterena metodom kapilarne elektroforeze. Efektivna elektroforetska pokretljivost je merena metodom kapilarne zonske elktroforeze u opsegu pH vrednosti od 4-11, pri konstantnoj jonskoj jačini (25 mM) i temperaturi (25 °C). U radu je korišćena neobložena kapilara (31,5 cm × 50 mm id) u koju su uzorci injektovani hidrodinamičkim putem pri 11 kV i praćeni na 200 nm. Aceton je upotrebljen kao marker elektroosmotskog toka. Merenjem efektivne elktroforetske pokretljivosti analita pri različitim pH vrednostima, metodom nelinearne regresione analize određene su pKa vrednosti jedinjenja. Termodinamičke kiselinske konstante ispitivanih jedinjenja su bile u opsegu od 6,21 za triamteren do 9,45 za efaroksan. Među derivatima 2-aminoimidazolina najizraženije bazne osobine ima klonidin sa pKa 8,02, dok moksonidin (pKa 7,35) i tizanidin (pKa 7,36) imaju nešto niže i veoma bliske pKa vrednosti.
Na osnovu dobijenih rezultata i poređenjem sa literaturnim podacima, metoda kapilarne elktroforeze se može koristiti kao brza, jednostavna i pouzdana metoda za određivanje pKa vrednosti srodnih jedinjenja.
PB  - Savez farmaceutskih udruženja Srbije
C3  - VI Kongres farmaceuta Srbije sa međunarodnim učešćem, Zbornik sažetaka
T1  - Determination of acidity constants of guanidine and imidazoline derivatives by capillary electrophoresis
T1  - Određivanje kiselinskih konstanti derivate gvanidina i imidazolina metodom kapilarne elktroforeze
SP  - 208
EP  - 209
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5201
ER  - 

@conference{
author = "Filipić, Slavica and Nikolić, Katarina and Popović, Gordana and Agbaba, Danica",
year = "2014",
abstract = "Guanidine and imidazoline derivatives belong to the family of imidazoline receptors ligands with diverse pharmacological effects on cardiovascular system. The presence of guanidine and imidazoline moieties gives them the properties of bases. Knowledge of their acidity constants (pKa values) and degree of ionization are important not only for analyitical procedures but also for their pharmacokinetic properties and activity. The main objective of this work was to determine the pKa values of 10 guanidine and imidazoline derivatives: moxonidine, clonidine, rilmenidine, tizanidine, idazoxan, efaroxan, guanfacine, harmane, harmine, and triamterene by capillary electrophoresis. The effective electrophoretic mobilities were measured by capillary zone electrophoresis in series of background electrolytes with broad pH range (4.00-11.00), with constant ionic strength (25 mM) and temperature (25 °C). All experiments were performed using an uncoated fused capillary (31.5 cm × 50 mm id). The samples were injected hydrodynamically at 11 kV and monitored at 200 nm. Acetone was used as marker of electroosmotic flow. The pKa values were determined by nonlinear regression analysis of the experimentally measured pH dependence of their effective electrophoretic mobilities. Thermodynamic pKa values of analysed compounds were estimated to be in the range from 6.21 for triamterene to 9.45 for efaroxan. Among 2-aminoimidazoline derivatives the strongest basic character posses clonidine with pKa 8.02 while moxonidine (pKa 7.35) and tizanidine (pKa 7.36) have slightly lower and very close pKa values. 
According to the obtained results and compared to the literature data capillary electrophoresis can be used as fast, simple and reliable method for determination of pKa values of related compounds., Derivati gvanidina i imidazolina pripadaju grupi liganada imidazolinskih receptora sa različitim farmakološkim efektima na kardiovaskularni sistem. Prisustvo gvanidina i imizolina u njihovoj strukturi daje im bazni karakter. Poznavanje kiselinskih konstanti (pKa vrednosti) i stepena jonizacije ove grupe jednjenja značajno je kako sa analitičkog aspekta, tako is a aspekta njihovih farmakokinetičkih osobina i dejstva. Cilj ovog rada bio je da se odrede pKa vrednosti 10 derivata gvanidina i imidazolina: moksonidina, klonidina, rilmenidina, tizanidina, idazoksana, efaroksana, gvanfacina, harmana, harmina i triamterena metodom kapilarne elektroforeze. Efektivna elektroforetska pokretljivost je merena metodom kapilarne zonske elktroforeze u opsegu pH vrednosti od 4-11, pri konstantnoj jonskoj jačini (25 mM) i temperaturi (25 °C). U radu je korišćena neobložena kapilara (31,5 cm × 50 mm id) u koju su uzorci injektovani hidrodinamičkim putem pri 11 kV i praćeni na 200 nm. Aceton je upotrebljen kao marker elektroosmotskog toka. Merenjem efektivne elktroforetske pokretljivosti analita pri različitim pH vrednostima, metodom nelinearne regresione analize određene su pKa vrednosti jedinjenja. Termodinamičke kiselinske konstante ispitivanih jedinjenja su bile u opsegu od 6,21 za triamteren do 9,45 za efaroksan. Među derivatima 2-aminoimidazolina najizraženije bazne osobine ima klonidin sa pKa 8,02, dok moksonidin (pKa 7,35) i tizanidin (pKa 7,36) imaju nešto niže i veoma bliske pKa vrednosti.
Na osnovu dobijenih rezultata i poređenjem sa literaturnim podacima, metoda kapilarne elktroforeze se može koristiti kao brza, jednostavna i pouzdana metoda za određivanje pKa vrednosti srodnih jedinjenja.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "VI Kongres farmaceuta Srbije sa međunarodnim učešćem, Zbornik sažetaka",
title = "Determination of acidity constants of guanidine and imidazoline derivatives by capillary electrophoresis, Određivanje kiselinskih konstanti derivate gvanidina i imidazolina metodom kapilarne elktroforeze",
pages = "208-209",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5201"
}

Filipić, S., Nikolić, K., Popović, G.,& Agbaba, D.. (2014). Determination of acidity constants of guanidine and imidazoline derivatives by capillary electrophoresis. in VI Kongres farmaceuta Srbije sa međunarodnim učešćem, Zbornik sažetaka
Savez farmaceutskih udruženja Srbije., 208-209.
https://hdl.handle.net/21.15107/rcub_farfar_5201

Filipić S, Nikolić K, Popović G, Agbaba D. Determination of acidity constants of guanidine and imidazoline derivatives by capillary electrophoresis. in VI Kongres farmaceuta Srbije sa međunarodnim učešćem, Zbornik sažetaka. 2014;:208-209.
https://hdl.handle.net/21.15107/rcub_farfar_5201 .

Filipić, Slavica, Nikolić, Katarina, Popović, Gordana, Agbaba, Danica, "Determination of acidity constants of guanidine and imidazoline derivatives by capillary electrophoresis" in VI Kongres farmaceuta Srbije sa međunarodnim učešćem, Zbornik sažetaka (2014):208-209,
https://hdl.handle.net/21.15107/rcub_farfar_5201 .

TY  - CONF
AU  - Popović, Marija
AU  - Grujić, Maja
AU  - Popović, Gordana
AU  - Agbaba, Danica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5017
AB  - In this study the pKa values of irbesartan, an angiotensin receptor blocker, were
determined by potentiometry and the effects of sodium dodecyl sulfate
(SDS) and cetyl trimethyl ammonium bromide (CTAB) on its protolytic
equilibria have been investigated. It was observed that shift in pKa values is
a result of complex electrostatic and hydrophobic interactions with the
micelar solutions. Based on the obtained results drug interactions with
biomolecules can be evaluated.
PB  - Society of Physical Chemists of Serbia
C3  - PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia
T1  - The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan
VL  - I
SP  - 1133
EP  - 1136
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5017
ER  - 

@conference{
author = "Popović, Marija and Grujić, Maja and Popović, Gordana and Agbaba, Danica",
year = "2014",
abstract = "In this study the pKa values of irbesartan, an angiotensin receptor blocker, were
determined by potentiometry and the effects of sodium dodecyl sulfate
(SDS) and cetyl trimethyl ammonium bromide (CTAB) on its protolytic
equilibria have been investigated. It was observed that shift in pKa values is
a result of complex electrostatic and hydrophobic interactions with the
micelar solutions. Based on the obtained results drug interactions with
biomolecules can be evaluated.",
publisher = "Society of Physical Chemists of Serbia",
journal = "PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia",
title = "The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan",
volume = "I",
pages = "1133-1136",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5017"
}

Popović, M., Grujić, M., Popović, G.,& Agbaba, D.. (2014). The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan. in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 1133-1136.
https://hdl.handle.net/21.15107/rcub_farfar_5017

Popović M, Grujić M, Popović G, Agbaba D. The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan. in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia. 2014;I:1133-1136.
https://hdl.handle.net/21.15107/rcub_farfar_5017 .

Popović, Marija, Grujić, Maja, Popović, Gordana, Agbaba, Danica, "The effects of anoinic and cationic surfactants on acid-base equilibria of irbesartan" in PHYSICAL CHEMISTRY 2014, 12th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 22-26, 2014 Belgrade, Serbia, I (2014):1133-1136,
https://hdl.handle.net/21.15107/rcub_farfar_5017 .