TY  - JOUR
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
AU  - Lazović, Saša
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5549
AB  - Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.
PB  - Springer
T2  - Journal of Analytical Chemistry
T1  - Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds
VL  - 79
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1134/S1061934824010076
ER  - 

@article{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica and Lazović, Saša",
year = "2024",
abstract = "Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.",
publisher = "Springer",
journal = "Journal of Analytical Chemistry",
title = "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds",
volume = "79",
number = "1",
pages = "95-104",
doi = "10.1134/S1061934824010076"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B., Vujić, Z.,& Lazović, S.. (2024). Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry
Springer., 79(1), 95-104.
https://doi.org/10.1134/S1061934824010076

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z, Lazović S. Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry. 2024;79(1):95-104.
doi:10.1134/S1061934824010076 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, Lazović, Saša, "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds" in Journal of Analytical Chemistry, 79, no. 1 (2024):95-104,
https://doi.org/10.1134/S1061934824010076 . .

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

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

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

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

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

TY  - JOUR
AU  - Savić, Jelena
AU  - Vitnik, Vesna
AU  - Obradović, Darija
AU  - Vitnik, Željko
AU  - Petrić, Vanja
AU  - Čkalovski, Teodora
AU  - Lazović, Saša
AU  - Crevar, Milkica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5444
AB  - The retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters RM0 , a, and C0 were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acids.
PB  - Springer
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids
VL  - 36
IS  - 5
SP  - 415
EP  - 423
DO  - 10.1007/s00764-023-00274-9
ER  - 

@article{
author = "Savić, Jelena and Vitnik, Vesna and Obradović, Darija and Vitnik, Željko and Petrić, Vanja and Čkalovski, Teodora and Lazović, Saša and Crevar, Milkica",
year = "2023",
abstract = "The retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters RM0 , a, and C0 were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acids.",
publisher = "Springer",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids",
volume = "36",
number = "5",
pages = "415-423",
doi = "10.1007/s00764-023-00274-9"
}

Savić, J., Vitnik, V., Obradović, D., Vitnik, Ž., Petrić, V., Čkalovski, T., Lazović, S.,& Crevar, M.. (2023). Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids. in Journal of Planar Chromatography - Modern TLC
Springer., 36(5), 415-423.
https://doi.org/10.1007/s00764-023-00274-9

Savić J, Vitnik V, Obradović D, Vitnik Ž, Petrić V, Čkalovski T, Lazović S, Crevar M. Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids. in Journal of Planar Chromatography - Modern TLC. 2023;36(5):415-423.
doi:10.1007/s00764-023-00274-9 .

Savić, Jelena, Vitnik, Vesna, Obradović, Darija, Vitnik, Željko, Petrić, Vanja, Čkalovski, Teodora, Lazović, Saša, Crevar, Milkica, "Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids" in Journal of Planar Chromatography - Modern TLC, 36, no. 5 (2023):415-423,
https://doi.org/10.1007/s00764-023-00274-9 . .

TY  - CONF
AU  - Obradović, Darija
AU  - Agbaba, Danica
AU  - Lazović, Saša
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5356
AB  - U uslovima su kojima su istovremeno prisutni dualni hidrofilni (HILIC) i reverzno-fazni (RP)
mehanizmi ispitan je retencioni profil liganada imidazolinskih i serotoninskih receptora (1).
Razmotreno je biomimetičko značenje parametra retencije (prevojna tačka), koji definišu uslove u
kojima dolazi do smene videćih mehanizama interakcije. Retencioni profil 43 liganada
imidazolinskih i serotoninskih receptora je ispitan na Acclaim Mixed-Mode HILIC-1 koloni. Kao
mobilna faza korišćena je smeša acetonitrila i 20 mM amonijum-acetata (pH 6). Hromatografsko
ponašanje definisano je kao zavisnost retencionog parametra logk u odnosu na udeo acetonitrila u
mobilnoj fazi (φ) korišćenjem multimodalne jednačine (2). Prevojna tačka HILIC/RP regiona
izračunata je kao minimalna vrednost dobijene funkcije. Uočeno je da dobijene vrednosti prevojne
tačke korelišu sa lipofilnom profilnom ispitivanih jedinjenja (r > 0.70), potencijalom vezivanja za
ukupne proteine plazme (r > 0.77), kao i procentom apsorpcije leka iz gastrointesinalnog trakta (r >
0.56). Fizičko-hemijske interakcije koje utiču na vezivanje ispitivanih jedinjenja za
arilhidrokarbonske receptore (NR.AhR) u organizmu, uključene u regulaciju toksikološkog
potencijala, takođe utiču i na vrednosti prevojne prevojne tačke (r > 0.60). Na osnovu dobijenih
rezultata, zaključuje se da se prevojna tačka dualnih HILIC/RP interakcija može uspešno primeniti u
preliminarnoj karakterizaciji biofarmaceutskog i farmakokinetičkog profila liganada imidazolinskih
i serotoninskih receptora.
AB  - The retention profile of imidazoline and serotonin receptor ligands was investigated in dual
hydrophilic (HILIC) and reversed-phase (RP) interaction mode (1). The biomimetic meaning of the
turining point that defines the switch between the leading retention mechanisms was discussed. The
retention profile of 43 imidazoline and serotonin receptor ligands was investigated on an Acclaim
Mixed-Mode HILIC-1 column. A mixture of acetonitrile and 20 mM ammonium acetate (pH 6) was
used as the mobile phase. The retention was defined as the change of the parameter logk in relation
to the volume fraction of acetonitrile in the mobile phase (φ) using the multimodal equation (2). The
turning point of the HILIC/RP region was calculated as the minimum value of the multimodal
equation. The obtained values of the turning point correlate with the lipophilic profile of the tested
compounds (r > 0.70), as well as with the binding potential for total plasma proteins (r > 0.77), and
the percentage of drug absorption from the gastrointestinal tract (r > 0.56). The physico-chemical
interactions that affect the binding of the tested compounds to arylhydrocarbon receptors (NR.AhR)
in the organism, involved in the regulation of toxicological potential, also affect the turning point
values (r > 0.60). It can be concluded that the turning point of dual HILIC/RP interactions can be
successfully applied in the preliminary characterization of the biopharmaceutical and
pharmacokinetic profile of imidazoline and serotonin receptor ligands.
PB  - Savez farmaceutskih udruženja Srbije
C3  - Arhiv za farmaciju
T1  - Prevojna HILIC/RP tačka - biomimetički retencioni parametar
T1  - Turning HILIC/RP point - biomimetic retention parameter
VL  - 73
IS  - Supp. 4
SP  - S95
EP  - S96
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5356
ER  - 

@conference{
author = "Obradović, Darija and Agbaba, Danica and Lazović, Saša",
year = "2023",
abstract = "U uslovima su kojima su istovremeno prisutni dualni hidrofilni (HILIC) i reverzno-fazni (RP)
mehanizmi ispitan je retencioni profil liganada imidazolinskih i serotoninskih receptora (1).
Razmotreno je biomimetičko značenje parametra retencije (prevojna tačka), koji definišu uslove u
kojima dolazi do smene videćih mehanizama interakcije. Retencioni profil 43 liganada
imidazolinskih i serotoninskih receptora je ispitan na Acclaim Mixed-Mode HILIC-1 koloni. Kao
mobilna faza korišćena je smeša acetonitrila i 20 mM amonijum-acetata (pH 6). Hromatografsko
ponašanje definisano je kao zavisnost retencionog parametra logk u odnosu na udeo acetonitrila u
mobilnoj fazi (φ) korišćenjem multimodalne jednačine (2). Prevojna tačka HILIC/RP regiona
izračunata je kao minimalna vrednost dobijene funkcije. Uočeno je da dobijene vrednosti prevojne
tačke korelišu sa lipofilnom profilnom ispitivanih jedinjenja (r > 0.70), potencijalom vezivanja za
ukupne proteine plazme (r > 0.77), kao i procentom apsorpcije leka iz gastrointesinalnog trakta (r >
0.56). Fizičko-hemijske interakcije koje utiču na vezivanje ispitivanih jedinjenja za
arilhidrokarbonske receptore (NR.AhR) u organizmu, uključene u regulaciju toksikološkog
potencijala, takođe utiču i na vrednosti prevojne prevojne tačke (r > 0.60). Na osnovu dobijenih
rezultata, zaključuje se da se prevojna tačka dualnih HILIC/RP interakcija može uspešno primeniti u
preliminarnoj karakterizaciji biofarmaceutskog i farmakokinetičkog profila liganada imidazolinskih
i serotoninskih receptora., The retention profile of imidazoline and serotonin receptor ligands was investigated in dual
hydrophilic (HILIC) and reversed-phase (RP) interaction mode (1). The biomimetic meaning of the
turining point that defines the switch between the leading retention mechanisms was discussed. The
retention profile of 43 imidazoline and serotonin receptor ligands was investigated on an Acclaim
Mixed-Mode HILIC-1 column. A mixture of acetonitrile and 20 mM ammonium acetate (pH 6) was
used as the mobile phase. The retention was defined as the change of the parameter logk in relation
to the volume fraction of acetonitrile in the mobile phase (φ) using the multimodal equation (2). The
turning point of the HILIC/RP region was calculated as the minimum value of the multimodal
equation. The obtained values of the turning point correlate with the lipophilic profile of the tested
compounds (r > 0.70), as well as with the binding potential for total plasma proteins (r > 0.77), and
the percentage of drug absorption from the gastrointestinal tract (r > 0.56). The physico-chemical
interactions that affect the binding of the tested compounds to arylhydrocarbon receptors (NR.AhR)
in the organism, involved in the regulation of toxicological potential, also affect the turning point
values (r > 0.60). It can be concluded that the turning point of dual HILIC/RP interactions can be
successfully applied in the preliminary characterization of the biopharmaceutical and
pharmacokinetic profile of imidazoline and serotonin receptor ligands.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Prevojna HILIC/RP tačka - biomimetički retencioni parametar, Turning HILIC/RP point - biomimetic retention parameter",
volume = "73",
number = "Supp. 4",
pages = "S95-S96",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5356"
}

Obradović, D., Agbaba, D.,& Lazović, S.. (2023). Prevojna HILIC/RP tačka - biomimetički retencioni parametar. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 73(Supp. 4), S95-S96.
https://hdl.handle.net/21.15107/rcub_farfar_5356

Obradović D, Agbaba D, Lazović S. Prevojna HILIC/RP tačka - biomimetički retencioni parametar. in Arhiv za farmaciju. 2023;73(Supp. 4):S95-S96.
https://hdl.handle.net/21.15107/rcub_farfar_5356 .

Obradović, Darija, Agbaba, Danica, Lazović, Saša, "Prevojna HILIC/RP tačka - biomimetički retencioni parametar" in Arhiv za farmaciju, 73, no. Supp. 4 (2023):S95-S96,
https://hdl.handle.net/21.15107/rcub_farfar_5356 .