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  - Pleiades Publishing
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 = "Pleiades Publishing",
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
Pleiades Publishing., 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 .

TY  - JOUR
AU  - Turković, Nemanja
AU  - Anđelković, Nastasija
AU  - Obradović, Darija
AU  - Vujić, Zorica
AU  - Ivković, Branka
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5031
AB  - Defining  the  interaction  of  newly  synthesized  compounds  with plasma proteins is an important step in the drug development process. Chromatographic techniques can be successfully used in predicting the biopharmaceutical and pharmacokinetic properties of newly synthesized compounds. The aim of this study is to investigate and isolate the most important molecular properties that affect the interaction of 20 newly synthesized chalcones and commercial compounds (lopinavir, ritonavir, darunavir and ivermectin) with human serum albumin (HSA). The retention behaviour of the selected compounds was tested on a CHIRALPAK®HSA column. A mixture of phosphate buffer (pH 7.0) and isopropanol (80:20 volume ratio) was used as the mobile phase, and the support vector method was used to form the quantitative structure retention relationship (QSRR) model. Based on the obtained values of retention parameters, it was observed that halogenated derivatives show the strongest, and methylated chalcone derivatives the weakest interaction with HSA. By correlating the retention and physicochemical properties of the tested compounds, it was  shown  that  the  structural  (SDSCH)  and  electronic  properties  (MAXQ, EEM_F1) groups have the greatest influence on the retention behaviour and the interaction of the tested compounds with HSA. The obtained QSRR model can be applied in the prediction of the retention characteristics of new, structurally related chalcone derivatives on HSA stationary phase.
AB  - Дефинисање интеракције новосинтетисаних једињења са протеинима плазме је важан корак у процесу развоја лекова. Хроматографске технике се могу успешнo користити у предикцији биофармацеутских и фармакокинетичких особина новосинтетисаних једињења. Циљ овог рада је испитивање и издвајање најзначајнијих молекулских особина које утичу на интеракцију  24  новосинтетисаних халкона и њима сродних једињења са хуманим серумским албумином  (HSA).  Ретенционо понашање одабраних једињења је испитано на  CHIRALPAK®HSA колони. Као мобилна фаза коришћена је смеша фосфатног пуфера (pH 7,0) и изопропанола (запр. однос 80:20). У формирању QSRR модела коришћена је метода вектора подршке. На основу добијених вредности ретенционих параметара уочено је да халогеновани деривати показују најјачу, а метиловани деривати халкона најслабију интеракцију са HSA. Доводећи у корелацију ретенцију ифизичко-хемијска својства испитиваних једињења показало се да структурне  (SDSCH)  и електронске особине  (MAXQ,EEM_F1)  група највише утичу на ретенционо понашање и интеракцију испитиваних једињења са HSA. Добијени QSRR модел се може применити у предикцији ретенционих карактеристика нових, структурно-сродних деривата халконана HSA стационарној фази.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin
T1  - Примена течне хроматографије у дефинисању интеракција новосинтетисаних халкона и сродних супстанци са хуманим серумским албуминима
VL  - 88
IS  - 7-8
SP  - 765
EP  - 776
DO  - 10.2298/JSC221212033T
ER  - 

@article{
author = "Turković, Nemanja and Anđelković, Nastasija and Obradović, Darija and Vujić, Zorica and Ivković, Branka",
year = "2023",
abstract = "Defining  the  interaction  of  newly  synthesized  compounds  with plasma proteins is an important step in the drug development process. Chromatographic techniques can be successfully used in predicting the biopharmaceutical and pharmacokinetic properties of newly synthesized compounds. The aim of this study is to investigate and isolate the most important molecular properties that affect the interaction of 20 newly synthesized chalcones and commercial compounds (lopinavir, ritonavir, darunavir and ivermectin) with human serum albumin (HSA). The retention behaviour of the selected compounds was tested on a CHIRALPAK®HSA column. A mixture of phosphate buffer (pH 7.0) and isopropanol (80:20 volume ratio) was used as the mobile phase, and the support vector method was used to form the quantitative structure retention relationship (QSRR) model. Based on the obtained values of retention parameters, it was observed that halogenated derivatives show the strongest, and methylated chalcone derivatives the weakest interaction with HSA. By correlating the retention and physicochemical properties of the tested compounds, it was  shown  that  the  structural  (SDSCH)  and  electronic  properties  (MAXQ, EEM_F1) groups have the greatest influence on the retention behaviour and the interaction of the tested compounds with HSA. The obtained QSRR model can be applied in the prediction of the retention characteristics of new, structurally related chalcone derivatives on HSA stationary phase., Дефинисање интеракције новосинтетисаних једињења са протеинима плазме је важан корак у процесу развоја лекова. Хроматографске технике се могу успешнo користити у предикцији биофармацеутских и фармакокинетичких особина новосинтетисаних једињења. Циљ овог рада је испитивање и издвајање најзначајнијих молекулских особина које утичу на интеракцију  24  новосинтетисаних халкона и њима сродних једињења са хуманим серумским албумином  (HSA).  Ретенционо понашање одабраних једињења је испитано на  CHIRALPAK®HSA колони. Као мобилна фаза коришћена је смеша фосфатног пуфера (pH 7,0) и изопропанола (запр. однос 80:20). У формирању QSRR модела коришћена је метода вектора подршке. На основу добијених вредности ретенционих параметара уочено је да халогеновани деривати показују најјачу, а метиловани деривати халкона најслабију интеракцију са HSA. Доводећи у корелацију ретенцију ифизичко-хемијска својства испитиваних једињења показало се да структурне  (SDSCH)  и електронске особине  (MAXQ,EEM_F1)  група највише утичу на ретенционо понашање и интеракцију испитиваних једињења са HSA. Добијени QSRR модел се може применити у предикцији ретенционих карактеристика нових, структурно-сродних деривата халконана HSA стационарној фази.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin, Примена течне хроматографије у дефинисању интеракција новосинтетисаних халкона и сродних супстанци са хуманим серумским албуминима",
volume = "88",
number = "7-8",
pages = "765-776",
doi = "10.2298/JSC221212033T"
}

Turković, N., Anđelković, N., Obradović, D., Vujić, Z.,& Ivković, B.. (2023). Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 88(7-8), 765-776.
https://doi.org/10.2298/JSC221212033T

Turković N, Anđelković N, Obradović D, Vujić Z, Ivković B. Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin. in Journal of the Serbian Chemical Society. 2023;88(7-8):765-776.
doi:10.2298/JSC221212033T .

Turković, Nemanja, Anđelković, Nastasija, Obradović, Darija, Vujić, Zorica, Ivković, Branka, "Application of liquid chromatography in defining the interaction of newly synthesized chalcones and related compounds with human serum albumin" in Journal of the Serbian Chemical Society, 88, no. 7-8 (2023):765-776,
https://doi.org/10.2298/JSC221212033T . .

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

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

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

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

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

TY  - JOUR
AU  - Obradović, Darija
AU  - Komsta, Lukasz
AU  - Stavrianidi Nikolaevič, Andrey
AU  - Shpigun Aleksejevič, Oleg
AU  - Pokrovskiy Igorevič, Oleg
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4250
AB  - The experimental design methodology based on central composite design of experiments was applied
to compare the retention mechanisms in supercritical fluid chromatography (SFC) and non-aqueous hy-
drophilic interaction liquid chromatography (NA-HILIC). The selected set consists of 26 compounds that
belong to imidazoline and serotonin receptor ligands. The different chemometric tools (multiple linear
regression, principal component analysis, parallel factor analysis) were used to examine the retention, as
well as to identify the most significant retention mechanisms. The retention mechanism was investigated
on two different stationary phases (diol, and mixed-mode diol). In NA-HILIC, the mobile phase contains
acetonitrile as a main component, and methanolic solution of ammonium formate (+ 0.1% of formic acid)
as a modifier. The same mobile phase modifier was used in SFC, with a difference in the main component
of the mobile phase which was CO2.
The retention behaviour differs significantly between HILIC and SFC conditions. The retention pattern
in HILIC mode was more partition-like, while in SFC the solute-sorbent interactions allowed retention.
The retention mechanism between mixed-mode diol and the diol phases varies depending on the applied
chromatographic mode, e.g., in HILIC the type of stationary phase significantly affects the elution order,
while in SFC this was not the case. The HILIC retention behaviour was influenced by the number of
tertiary amines-aliphatic, and N atom-centred fragments in tested compounds. On the other hand, the
number of pyrrole and pyridine rings in the structure of the compound showed correlation with their
SFC retention, simultaneously increasing the molecular weight and rapid elution of larger compounds. It
was found that temperature surprisingly plays a major role in SFC mode. The increase in temperature
reduces the relative contribution of enthalpy factors to total retention, so the separation in SFC was more
entropy-controlled. For further pharmaceutical research and optimization, the SFC would be considered
more beneficial compared to HILIC since it gives good selectivity in separation of chosen impurities.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - Retention mechanisms of imidazolin and piperazine-related compounds in non-aqueous hydrophilic interaction and supercritical fluid chromatography based on chemometric design and analysis
VL  - 1678
DO  - 10.1016/j.chroma.2022.463340
ER  - 

@article{
author = "Obradović, Darija and Komsta, Lukasz and Stavrianidi Nikolaevič, Andrey and Shpigun Aleksejevič, Oleg and Pokrovskiy Igorevič, Oleg and Vujić, Zorica",
year = "2022",
abstract = "The experimental design methodology based on central composite design of experiments was applied
to compare the retention mechanisms in supercritical fluid chromatography (SFC) and non-aqueous hy-
drophilic interaction liquid chromatography (NA-HILIC). The selected set consists of 26 compounds that
belong to imidazoline and serotonin receptor ligands. The different chemometric tools (multiple linear
regression, principal component analysis, parallel factor analysis) were used to examine the retention, as
well as to identify the most significant retention mechanisms. The retention mechanism was investigated
on two different stationary phases (diol, and mixed-mode diol). In NA-HILIC, the mobile phase contains
acetonitrile as a main component, and methanolic solution of ammonium formate (+ 0.1% of formic acid)
as a modifier. The same mobile phase modifier was used in SFC, with a difference in the main component
of the mobile phase which was CO2.
The retention behaviour differs significantly between HILIC and SFC conditions. The retention pattern
in HILIC mode was more partition-like, while in SFC the solute-sorbent interactions allowed retention.
The retention mechanism between mixed-mode diol and the diol phases varies depending on the applied
chromatographic mode, e.g., in HILIC the type of stationary phase significantly affects the elution order,
while in SFC this was not the case. The HILIC retention behaviour was influenced by the number of
tertiary amines-aliphatic, and N atom-centred fragments in tested compounds. On the other hand, the
number of pyrrole and pyridine rings in the structure of the compound showed correlation with their
SFC retention, simultaneously increasing the molecular weight and rapid elution of larger compounds. It
was found that temperature surprisingly plays a major role in SFC mode. The increase in temperature
reduces the relative contribution of enthalpy factors to total retention, so the separation in SFC was more
entropy-controlled. For further pharmaceutical research and optimization, the SFC would be considered
more beneficial compared to HILIC since it gives good selectivity in separation of chosen impurities.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "Retention mechanisms of imidazolin and piperazine-related compounds in non-aqueous hydrophilic interaction and supercritical fluid chromatography based on chemometric design and analysis",
volume = "1678",
doi = "10.1016/j.chroma.2022.463340"
}

Obradović, D., Komsta, L., Stavrianidi Nikolaevič, A., Shpigun Aleksejevič, O., Pokrovskiy Igorevič, O.,& Vujić, Z.. (2022). Retention mechanisms of imidazolin and piperazine-related compounds in non-aqueous hydrophilic interaction and supercritical fluid chromatography based on chemometric design and analysis. in Journal of Chromatography A
Elsevier B.V.., 1678.
https://doi.org/10.1016/j.chroma.2022.463340

Obradović D, Komsta L, Stavrianidi Nikolaevič A, Shpigun Aleksejevič O, Pokrovskiy Igorevič O, Vujić Z. Retention mechanisms of imidazolin and piperazine-related compounds in non-aqueous hydrophilic interaction and supercritical fluid chromatography based on chemometric design and analysis. in Journal of Chromatography A. 2022;1678.
doi:10.1016/j.chroma.2022.463340 .

Obradović, Darija, Komsta, Lukasz, Stavrianidi Nikolaevič, Andrey, Shpigun Aleksejevič, Oleg, Pokrovskiy Igorevič, Oleg, Vujić, Zorica, "Retention mechanisms of imidazolin and piperazine-related compounds in non-aqueous hydrophilic interaction and supercritical fluid chromatography based on chemometric design and analysis" in Journal of Chromatography A, 1678 (2022),
https://doi.org/10.1016/j.chroma.2022.463340 . .

TY  - JOUR
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, J.
AU  - Kowalska, T.
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4182
AB  - We investigated and compared hydrophilic retention mechanism (HILIC) of ten compounds (imidazoline and serotonin receptor ligands) in the thin-layer chromatographic (TLC) system and the high-performance liquid chromatographic (HPLC) system. The TLC and HPLC stationary phases were the chemically bonded amino (NH2) phases. In the TLC mode, the binary mobile phases were composed of acetonitrile (as the main component) and water or methanol (as the modifier). In the HPLC mode, the binary mobile phase was composed of acetonitrile (as the main component) and methanol (as the modifier). For each compound, we determined this region for which linear relationship between the retention and volume fraction of the mobile phase modifier was observed, and the retention behaviour was described by the linear solvent strength (LSS) model. With the obtained regression constant values (log k0, RM0) in mind, we selected molecular parameters influencing retention mechanism in the considered chromatographic systems. Lipophilicity plays an important role in the TLC mode with the acetonitrile‒methanol mobile phase, while geometrical characteristics of the test compounds (ring complexity, number of multiple bonds) play a predominant role in the TLC mode with the acetonitrile‒water mobile phase. It was also established that the hydrophilic mechanisms are different for the non-aqueous TLC vs. aqueous TLC systems and for the TLC vs. HPLC systems. As a result, different elution orders and separation performances can be expected for the imidazoline and serotonin receptor ligands, depending on the chromatographic system employed.
PB  - Springer
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems
VL  - 35
IS  - 3
SP  - 251
EP  - 263
DO  - 10.1007/s00764-022-00172-6
ER  - 

@article{
author = "Obradović, Darija and Savić, Jelena and Joksimović, J. and Kowalska, T. and Agbaba, Danica",
year = "2022",
abstract = "We investigated and compared hydrophilic retention mechanism (HILIC) of ten compounds (imidazoline and serotonin receptor ligands) in the thin-layer chromatographic (TLC) system and the high-performance liquid chromatographic (HPLC) system. The TLC and HPLC stationary phases were the chemically bonded amino (NH2) phases. In the TLC mode, the binary mobile phases were composed of acetonitrile (as the main component) and water or methanol (as the modifier). In the HPLC mode, the binary mobile phase was composed of acetonitrile (as the main component) and methanol (as the modifier). For each compound, we determined this region for which linear relationship between the retention and volume fraction of the mobile phase modifier was observed, and the retention behaviour was described by the linear solvent strength (LSS) model. With the obtained regression constant values (log k0, RM0) in mind, we selected molecular parameters influencing retention mechanism in the considered chromatographic systems. Lipophilicity plays an important role in the TLC mode with the acetonitrile‒methanol mobile phase, while geometrical characteristics of the test compounds (ring complexity, number of multiple bonds) play a predominant role in the TLC mode with the acetonitrile‒water mobile phase. It was also established that the hydrophilic mechanisms are different for the non-aqueous TLC vs. aqueous TLC systems and for the TLC vs. HPLC systems. As a result, different elution orders and separation performances can be expected for the imidazoline and serotonin receptor ligands, depending on the chromatographic system employed.",
publisher = "Springer",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems",
volume = "35",
number = "3",
pages = "251-263",
doi = "10.1007/s00764-022-00172-6"
}

Obradović, D., Savić, J., Joksimović, J., Kowalska, T.,& Agbaba, D.. (2022). Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems. in Journal of Planar Chromatography - Modern TLC
Springer., 35(3), 251-263.
https://doi.org/10.1007/s00764-022-00172-6

Obradović D, Savić J, Joksimović J, Kowalska T, Agbaba D. Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems. in Journal of Planar Chromatography - Modern TLC. 2022;35(3):251-263.
doi:10.1007/s00764-022-00172-6 .

Obradović, Darija, Savić, Jelena, Joksimović, J., Kowalska, T., Agbaba, Danica, "Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems" in Journal of Planar Chromatography - Modern TLC, 35, no. 3 (2022):251-263,
https://doi.org/10.1007/s00764-022-00172-6 . .

TY  - JOUR
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Obradović, Darija
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3989
AB  - Permeability assessment of small molecules through the blood-brain barrier (BBB) plays a significant role in the development of effective central nervous system (CNS) drug candidates. Since in vivo methods for BBB permeability estimation require a lot of time and resources, in silico and in vitro approaches are becoming increasingly popular nowadays for faster and more economical predictions in early phases of drug discovery. In this work, through application of in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and in silico computational methods we aimed to examine the passive permeability of eighteen compounds, which affect serotonin and dopamine levels in the CNS. The data set was consisted of novel six human dopamine transporter (hDAT) substrates that were previously identified as the most promising lead compounds for further optimisation to achieve neuroprotective effect, twelve approved CNS drugs, and their related compounds. Firstly, PAMPA methods was used to experimentally determine effective BBB permeability (Pe) for all studied compounds and obtained results were further submitted for quantitative structure permeability relationship (QSPR) analysis. QSPR models were built by using three different statistical methods: stepwise multiple linear regression (MLR), partial least square (PLS), and support-vector machine (SVM), while their predictive capability was tested through internal and external validation. Obtained statistical parameters (MLR- R2pred=-0.10; PLS- R2pred=0.64, r2m=0.69, r/2m=0.44; SVM- R2pred=0.57, r2m=0.72, r/2m=0.55) indicated that the SVM model is superior over others. The most important molecular descriptors (H0p and SolvEMt_3D) were identified and used to propose structural modifications of the examined compounds in order to improve their BBB permeability. Moreover, steered molecular dynamics (SMD) simulation was employed to comprehensively investigate the permeability pathway of compounds through a lipid bilayer. Taken together, the created QSPR model could be used as a reliable and fast pre-screening tool for BBB permeability prediction of structurally related CNS compounds, while performed MD simulations provide a good foundation for future in silico examination.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates
VL  - 168
DO  - 10.1016/j.ejps.2021.106056
ER  - 

@article{
author = "Radan, Milica and Đikić, Teodora and Obradović, Darija and Nikolić, Katarina",
year = "2022",
abstract = "Permeability assessment of small molecules through the blood-brain barrier (BBB) plays a significant role in the development of effective central nervous system (CNS) drug candidates. Since in vivo methods for BBB permeability estimation require a lot of time and resources, in silico and in vitro approaches are becoming increasingly popular nowadays for faster and more economical predictions in early phases of drug discovery. In this work, through application of in vitro parallel artificial membrane permeability assay (PAMPA-BBB) and in silico computational methods we aimed to examine the passive permeability of eighteen compounds, which affect serotonin and dopamine levels in the CNS. The data set was consisted of novel six human dopamine transporter (hDAT) substrates that were previously identified as the most promising lead compounds for further optimisation to achieve neuroprotective effect, twelve approved CNS drugs, and their related compounds. Firstly, PAMPA methods was used to experimentally determine effective BBB permeability (Pe) for all studied compounds and obtained results were further submitted for quantitative structure permeability relationship (QSPR) analysis. QSPR models were built by using three different statistical methods: stepwise multiple linear regression (MLR), partial least square (PLS), and support-vector machine (SVM), while their predictive capability was tested through internal and external validation. Obtained statistical parameters (MLR- R2pred=-0.10; PLS- R2pred=0.64, r2m=0.69, r/2m=0.44; SVM- R2pred=0.57, r2m=0.72, r/2m=0.55) indicated that the SVM model is superior over others. The most important molecular descriptors (H0p and SolvEMt_3D) were identified and used to propose structural modifications of the examined compounds in order to improve their BBB permeability. Moreover, steered molecular dynamics (SMD) simulation was employed to comprehensively investigate the permeability pathway of compounds through a lipid bilayer. Taken together, the created QSPR model could be used as a reliable and fast pre-screening tool for BBB permeability prediction of structurally related CNS compounds, while performed MD simulations provide a good foundation for future in silico examination.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates",
volume = "168",
doi = "10.1016/j.ejps.2021.106056"
}

Radan, M., Đikić, T., Obradović, D.,& Nikolić, K.. (2022). Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 168.
https://doi.org/10.1016/j.ejps.2021.106056

Radan M, Đikić T, Obradović D, Nikolić K. Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates. in European Journal of Pharmaceutical Sciences. 2022;168.
doi:10.1016/j.ejps.2021.106056 .

Radan, Milica, Đikić, Teodora, Obradović, Darija, Nikolić, Katarina, "Application of in vitro PAMPA technique and in silico computational methods for blood-brain barrier permeability prediction of novel CNS drug candidates" in European Journal of Pharmaceutical Sciences, 168 (2022),
https://doi.org/10.1016/j.ejps.2021.106056 . .

TY  - CONF
AU  - Obradović, Darija
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4604
AB  - The characterization of drug-protein plasma interactions is a routinely performed
part of drug discovery process. The unbound concentration of the drug depends on the
binding affinity to plasma proteins, which consequently affects its therapeutic effect,
absorption, distribution, metabolism and excretion (1). The most important plasma proteins
are human serum albumin (HSA), lipoproteins and alpha-1 acid glycoproteins (AGP). The
liquid chromatography can be successfully used for in vitro estimation of plasma protein
binding affinity using HSA or AGP modified silica gel as a stationary phase (2). The
interaction with HSA has been tested for a wide range of 33 pharmacologically active
compounds including dipeptidyl peptidase IV inhibitors, angiotensin-converting enzyme
inhibitors, β-blockers, calcium channel blockers and serotonin/dopamine receptor ligands
under reversed-phase conditions. The drug-HSA interaction was interpreted by using the
retention modeling, and by selecting the most significant structural characteristics that have
an influence on the retention mechanism. The small structural differences, which are
reflected in different lipophilicity and polarity, affect the drug-HSA interaction. The retention
of the compounds was successfully defined by using the quadratic equation. The isocratic
(logk(14%)) and extrapolated factors (b0(LSS)) showed a high correlation with the
experimentally available data, and in silico estimated affinity for HSA. The structural
properties and charged parts of the molecule surface have been found to significantly affect
the HSA mechanism. The obtained results can be successfully applied in further optimization
of the structural characteristics of the newly synthesized compounds in order to achieve the
desired therapeutic and pharmacokinetic effect.
AB  - Karakterizacija interakcije novosintetisanih jedinjenja sa plazma proteinima je
rutinski deo procesa proizvodnje i otkića novih lekova. Slobodna koncentracije lekovite
supstance zavisi od stepena vezivanja za proteine plazme, što posledično utiče na njen
terapijski efekat, apsorpciju, distribuciju, metabolizam i izlučivanje (1). Najznačajniji plazma
proteini su humani serumski albumin (HSA), lipoproteini i alfa-1 kiseli glikoproteini (AGP).
Tečna hromatografija se uspešno koristi za in vitro procenu afiniteta vezivanja lekovite
supstance za plazma proteine primenom modifikovane silika gel stacionarne faze sa HSA-om
ili AGP-om, i korišćenjem mobilne faze čiji sastav simulira fiziološke uslove (2). Za širok
spektar 33 farmakološki aktivnih jedinjenja koja uključuju inhibitore dipeptidil peptidaze IV,
inhibitore angiotenzin konvertujućeg enzima, β-blokatore, blokatore kalcijumovih kanala i
ligande serotoninskih/dopaminskih receptora ispitana je interakcija sa HSA-om u uslovima
reverzno-fazne tečne hromatografije. Lek-plazma protein interakcija je definisana na osnovu
mehanizma zadržavanja na HSA stacionarnoj fazi, primenom metode retencionog
modelovanja, kao i izdavajanjem najznačajnijih strukturnih karakteristika koje utiču na
retenciono ponašanje. Utvrđeno je da male strukturne razlike, koje se ogledaju u različitoj
lipofilnosti i polarnosti, utiču na interakciju sa HSA-om. Kvadratnim modelom je uspešno
definisano retenciono ponašanje ispitivanih jedinjenja. Izokratski (logk(14%)) i
ekstrapolisani retencioni faktor (b0(LSS)) su pokazali visok stepen slaganja sa
eksperimentalno dostupnim i in silico procenjenim afinitetom za HSA. Ustanovljeno je da
strukturna svojstva (broj dvostrukih veza, aromatični prstenovi, benzil, arlil supstituenti) i
naleketrisani fragmenti površine molekula značajno utiču na HSA interakciju. Dobijeni
rezultati se mogu uspešno primeniti u daljoj optimizaciji strukturnih karakteristika
novosintetisanih jedinjenja i postizanja željenih terapijskih i farmakokinetičkih ciljeva.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - In vitro estimation and characterization of drug-plasma protein interaction
T1  - In vitro procena i karakterizacija lek‐plazma protein interakcije
VL  - 72
IS  - 4 suplement
SP  - S546
EP  - S547
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4604
ER  - 

@conference{
author = "Obradović, Darija and Vujić, Zorica",
year = "2022",
abstract = "The characterization of drug-protein plasma interactions is a routinely performed
part of drug discovery process. The unbound concentration of the drug depends on the
binding affinity to plasma proteins, which consequently affects its therapeutic effect,
absorption, distribution, metabolism and excretion (1). The most important plasma proteins
are human serum albumin (HSA), lipoproteins and alpha-1 acid glycoproteins (AGP). The
liquid chromatography can be successfully used for in vitro estimation of plasma protein
binding affinity using HSA or AGP modified silica gel as a stationary phase (2). The
interaction with HSA has been tested for a wide range of 33 pharmacologically active
compounds including dipeptidyl peptidase IV inhibitors, angiotensin-converting enzyme
inhibitors, β-blockers, calcium channel blockers and serotonin/dopamine receptor ligands
under reversed-phase conditions. The drug-HSA interaction was interpreted by using the
retention modeling, and by selecting the most significant structural characteristics that have
an influence on the retention mechanism. The small structural differences, which are
reflected in different lipophilicity and polarity, affect the drug-HSA interaction. The retention
of the compounds was successfully defined by using the quadratic equation. The isocratic
(logk(14%)) and extrapolated factors (b0(LSS)) showed a high correlation with the
experimentally available data, and in silico estimated affinity for HSA. The structural
properties and charged parts of the molecule surface have been found to significantly affect
the HSA mechanism. The obtained results can be successfully applied in further optimization
of the structural characteristics of the newly synthesized compounds in order to achieve the
desired therapeutic and pharmacokinetic effect., Karakterizacija interakcije novosintetisanih jedinjenja sa plazma proteinima je
rutinski deo procesa proizvodnje i otkića novih lekova. Slobodna koncentracije lekovite
supstance zavisi od stepena vezivanja za proteine plazme, što posledično utiče na njen
terapijski efekat, apsorpciju, distribuciju, metabolizam i izlučivanje (1). Najznačajniji plazma
proteini su humani serumski albumin (HSA), lipoproteini i alfa-1 kiseli glikoproteini (AGP).
Tečna hromatografija se uspešno koristi za in vitro procenu afiniteta vezivanja lekovite
supstance za plazma proteine primenom modifikovane silika gel stacionarne faze sa HSA-om
ili AGP-om, i korišćenjem mobilne faze čiji sastav simulira fiziološke uslove (2). Za širok
spektar 33 farmakološki aktivnih jedinjenja koja uključuju inhibitore dipeptidil peptidaze IV,
inhibitore angiotenzin konvertujućeg enzima, β-blokatore, blokatore kalcijumovih kanala i
ligande serotoninskih/dopaminskih receptora ispitana je interakcija sa HSA-om u uslovima
reverzno-fazne tečne hromatografije. Lek-plazma protein interakcija je definisana na osnovu
mehanizma zadržavanja na HSA stacionarnoj fazi, primenom metode retencionog
modelovanja, kao i izdavajanjem najznačajnijih strukturnih karakteristika koje utiču na
retenciono ponašanje. Utvrđeno je da male strukturne razlike, koje se ogledaju u različitoj
lipofilnosti i polarnosti, utiču na interakciju sa HSA-om. Kvadratnim modelom je uspešno
definisano retenciono ponašanje ispitivanih jedinjenja. Izokratski (logk(14%)) i
ekstrapolisani retencioni faktor (b0(LSS)) su pokazali visok stepen slaganja sa
eksperimentalno dostupnim i in silico procenjenim afinitetom za HSA. Ustanovljeno je da
strukturna svojstva (broj dvostrukih veza, aromatični prstenovi, benzil, arlil supstituenti) i
naleketrisani fragmenti površine molekula značajno utiču na HSA interakciju. Dobijeni
rezultati se mogu uspešno primeniti u daljoj optimizaciji strukturnih karakteristika
novosintetisanih jedinjenja i postizanja željenih terapijskih i farmakokinetičkih ciljeva.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "In vitro estimation and characterization of drug-plasma protein interaction, In vitro procena i karakterizacija lek‐plazma protein interakcije",
volume = "72",
number = "4 suplement",
pages = "S546-S547",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4604"
}

Obradović, D.,& Vujić, Z.. (2022). In vitro estimation and characterization of drug-plasma protein interaction. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S546-S547.
https://hdl.handle.net/21.15107/rcub_farfar_4604

Obradović D, Vujić Z. In vitro estimation and characterization of drug-plasma protein interaction. in Arhiv za farmaciju. 2022;72(4 suplement):S546-S547.
https://hdl.handle.net/21.15107/rcub_farfar_4604 .

Obradović, Darija, Vujić, Zorica, "In vitro estimation and characterization of drug-plasma protein interaction" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S546-S547,
https://hdl.handle.net/21.15107/rcub_farfar_4604 .

TY  - CONF
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4605
AB  - The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied.
AB  - Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography
T1  - Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji
VL  - 72
IS  - 4 suplement
SP  - S548
EP  - S549
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4605
ER  - 

@conference{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica",
year = "2022",
abstract = "The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied., Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography, Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji",
volume = "72",
number = "4 suplement",
pages = "S548-S549",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4605"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B.,& Vujić, Z.. (2022). Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z. Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju. 2022;72(4 suplement):S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S548-S549,
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

TY  - THES
AU  - Obradović, Darija
PY  - 2021
UR  - https://uvidok.rcub.bg.ac.rs/bitstream/handle/123456789/4262/Referat.pdf
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=8414
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:24646/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=48981257
UR  - https://nardus.mpn.gov.rs/handle/123456789/18776
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4033
AB  - U ovoj doktorskoj disertaciji ispitano je retenciono ponašanje liganada imidazolinskih/α-adrenergičkih receptora, liganada serotoninskih receptora i srodnih jedinjenja. Obe grupe ispitivanih jedinjenja osnovnim ili sporednim mehanizmima deluju na centralni nervni sistem. Retencione karakteristike odabranih jedinjenja su ispitane primenom hromatografije hidrofilnih interakcija (HILIC), reverzno-fazne tečne hromatografije (RP-LC) i superkritične fluidne hromatografije (SFC) na polarnim stacionarnim fazama.Proces istraživanja obuhvatio je karakterizaciju retencionih mehanizama primenom linearnih retencionih modela i procenu uticaja ukupne polarnosti mobilne faze na retenciono ponašanje. Uvedeni su novi parametri retencije i formirani modeli za predviđanje retencionog ponašanja na mixed-mode stacionarnoj fazi u odnosu na fizičko-hemijske osobine ispitivanih jedinjenja, kao i karakteristike mobilne faze. U hromatografskim sistemima u kojima dolazi do smene između HILIC i RP retencionih mehanizama, predložene su nove jednačine za definisanje i predviđanje vrednosti prevojne tačke. Parametri retencije su detaljno ispitani u SFC i HILIC sistemima, i izdvojene molekulske osobine sa najvećim uticajem na retencioni mehanizam. Takođe, u SFC-u je primenjena metodologija eksperimentalnog dizajna za definisanje retencionih karakteristika.Formirani modeli omogućuju pouzdano predviđanje retencionog ponašanja novosintetisanih liganada imidazolinskih i serotoninskih receptora i strukturno srodnih jedinjenja u različitim hromatografskim uslovima. Dobijeni rezultati su pokazali da se testirani hromatografski sistemi mogu uspešno primeniti u farmaceutskim ispitivanjima.
AB  - In this doctoral dissertation, retention behaviour was investigated of imidazoline/α-adrenergic receptor ligands, serotonin receptor ligands and their related compounds. Both groups of investigated compounds exert an effect on central nervous system by the primary or secondary mechanism. Retention characteristic of the selected compounds on polar stationary phases was examined for hydrophilic interaction chromatography (HILIC), reversed-phase liquid chromatography (RP-LC), and supercritical fluid chromatography (SFC).The research included characterization of retention mechanisms with use of the linear retention models and an assessment of the influence of total polarity of mobile phase on retention behaviour. Novel retention parameters were introduced and models were deviced to predict retention behaviour in the mixed-mode chromatography systems, taking into the account physico-chemical properties of tested compounds and mobile phase characteristics. The turning point was defined for chromatographic systems characterizing with the bimodal HILIC/RP retention mechanisms and novel equations were proposed for prediction of the turining point values. Retention behaviour was investigated under the HILIC and SFC conditions, and the most important molecular properties governing retention were selected. In the case of SFC, the experimental design methodology was also applied to describe analyte retention.The proposed models allow a reliable prediction of retention behaviour for the newly synthesized imidazoline and serotonin receptors ligands and their structurally related compounds. The obtained results show that the investigated chromatographic systems can successfully be applied to pharmaceutical investigations.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora i srodnih jedinjenja u različitim hromatografskim uslovima
UR  - https://hdl.handle.net/21.15107/rcub_nardus_18776
ER  - 

@phdthesis{
author = "Obradović, Darija",
year = "2021",
abstract = "U ovoj doktorskoj disertaciji ispitano je retenciono ponašanje liganada imidazolinskih/α-adrenergičkih receptora, liganada serotoninskih receptora i srodnih jedinjenja. Obe grupe ispitivanih jedinjenja osnovnim ili sporednim mehanizmima deluju na centralni nervni sistem. Retencione karakteristike odabranih jedinjenja su ispitane primenom hromatografije hidrofilnih interakcija (HILIC), reverzno-fazne tečne hromatografije (RP-LC) i superkritične fluidne hromatografije (SFC) na polarnim stacionarnim fazama.Proces istraživanja obuhvatio je karakterizaciju retencionih mehanizama primenom linearnih retencionih modela i procenu uticaja ukupne polarnosti mobilne faze na retenciono ponašanje. Uvedeni su novi parametri retencije i formirani modeli za predviđanje retencionog ponašanja na mixed-mode stacionarnoj fazi u odnosu na fizičko-hemijske osobine ispitivanih jedinjenja, kao i karakteristike mobilne faze. U hromatografskim sistemima u kojima dolazi do smene između HILIC i RP retencionih mehanizama, predložene su nove jednačine za definisanje i predviđanje vrednosti prevojne tačke. Parametri retencije su detaljno ispitani u SFC i HILIC sistemima, i izdvojene molekulske osobine sa najvećim uticajem na retencioni mehanizam. Takođe, u SFC-u je primenjena metodologija eksperimentalnog dizajna za definisanje retencionih karakteristika.Formirani modeli omogućuju pouzdano predviđanje retencionog ponašanja novosintetisanih liganada imidazolinskih i serotoninskih receptora i strukturno srodnih jedinjenja u različitim hromatografskim uslovima. Dobijeni rezultati su pokazali da se testirani hromatografski sistemi mogu uspešno primeniti u farmaceutskim ispitivanjima., In this doctoral dissertation, retention behaviour was investigated of imidazoline/α-adrenergic receptor ligands, serotonin receptor ligands and their related compounds. Both groups of investigated compounds exert an effect on central nervous system by the primary or secondary mechanism. Retention characteristic of the selected compounds on polar stationary phases was examined for hydrophilic interaction chromatography (HILIC), reversed-phase liquid chromatography (RP-LC), and supercritical fluid chromatography (SFC).The research included characterization of retention mechanisms with use of the linear retention models and an assessment of the influence of total polarity of mobile phase on retention behaviour. Novel retention parameters were introduced and models were deviced to predict retention behaviour in the mixed-mode chromatography systems, taking into the account physico-chemical properties of tested compounds and mobile phase characteristics. The turning point was defined for chromatographic systems characterizing with the bimodal HILIC/RP retention mechanisms and novel equations were proposed for prediction of the turining point values. Retention behaviour was investigated under the HILIC and SFC conditions, and the most important molecular properties governing retention were selected. In the case of SFC, the experimental design methodology was also applied to describe analyte retention.The proposed models allow a reliable prediction of retention behaviour for the newly synthesized imidazoline and serotonin receptors ligands and their structurally related compounds. The obtained results show that the investigated chromatographic systems can successfully be applied to pharmaceutical investigations.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora i srodnih jedinjenja u različitim hromatografskim uslovima",
url = "https://hdl.handle.net/21.15107/rcub_nardus_18776"
}

Obradović, D.. (2021). Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora i srodnih jedinjenja u različitim hromatografskim uslovima. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_18776

Obradović D. Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora i srodnih jedinjenja u različitim hromatografskim uslovima. in Универзитет у Београду. 2021;.
https://hdl.handle.net/21.15107/rcub_nardus_18776 .

Obradović, Darija, "Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora i srodnih jedinjenja u različitim hromatografskim uslovima" in Универзитет у Београду (2021),
https://hdl.handle.net/21.15107/rcub_nardus_18776 .

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

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

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

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

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

TY  - CONF
AU  - Obradović, Darija
AU  - Nikolaevich Stavrianidi, Andrey
AU  - Alekseevich Shpigun, Oleg
AU  - Agbaba, Danica
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4681
AB  - A possibility of predicting retention behaviour without a large number of preliminary
experiments is a significant segment of theoretical and experimental investigations. By using
an appropriate design to define experimental conditions (Design of Experiments, DoE), the
retention behaviour of compounds can be described as a function of the most important
parameters of chromatographic system. Further, the DoE methodology has shown successful
applicability to modeling retention under the environmentally friendly Supercritical Fluid
Chromatography (SFC) conditions (1). In the last decades, robustness of the SFC instruments
has been improved in order to minimize ecological risks, and routine application of the SFC
technique has been introduced into many pharmaceutical strategies (e.g., the Good
Manufacturing Practice, GMP) (2). Therefore, the aim of our study was to define the influence
of the main chromatographic factors on the retention behaviour of fourteen imidazoline and
serotonin receptor ligands under the SFC conditions. Using the Central Composite Design
(CCD) approach, retention characteristics (k) of the test compounds were examined on the
mixed-mode stationary phase, with the mixture of supercritical CO2 and methanolic
ammonium-formate (with an addition of 0.1% formic acid) used as mobile phase. We took into
the consideration the influence of the following factors: volume fraction of methanol in mobile
phase (20-30 %), ammonium-formate concentration (15-25 mM), and temperature deviation
(20-30 °C). The most important chromatographic factors were selected by the step-wise
multilinear regression (MLR), and their statistical significance was assessed using the ANOVA
analysis. Based on the results obtained, it was established that the retention characteristics
were significantly influenced by changing the methanol and ammonium-formate
concentrations in mobile phase (r > 0.90, p < 0.05), Figure 1. High degree of agreement (r >
0.98) was observed, when the theoretically predicted logk values for 35% and 15% volume
fraction of methanol in mobile phase were compared with the experimental ones. The
obtained results confirm successful applicability of the experimental design methodology in
order to perform a minimum number of experiments, as demonstrated upon an example of
modeling and predicting the retention behaviour of imidazoline and serotonin receptor
ligands under the SFC conditions.
AB  - Mogućnost predviđanja retencije u odsustvu velikog broja prethodnih eksperimenata,
značajan je segment teorijskih i eksperimentalnih ispitivanja. Odgovarajućim dizajnom
eksperimentalnih uslova (Design of Experiments, DoE), a na osnovu minimalnog broja
eksperimenata, može se definisati retenciono ponašanje jedinjenja u funkciji najznačajnijih
parametara hromatografskog sistema. Primena DoE metodologije je takođe zabeležena i
prilikom modelovanja retencije u uslovima ekološki bezbedne, superkritične fluidne
hromatografije (Supercritical Fluid Chromatography, SFC) (1). Zbog minimalnih ekoloških
rizika, robusnost SFC instrumenata je poboljšana, a rutinska primena SFC tehnike je uvedena
i u regulatorne farmaceutske propise (npr. dobra proizvođačka praksa; Good Manufacturing
Practice-GMP) (2). Na osnovu toga, cilj ovog istraživanja obuhvatio je definisanje uticaja
najznačajnijih faktora hromatografskog sistema na retenciono ponašanje 14 odabranih
liganada imidazolinskih i serotoninskih receptora na mixed-mode stacionarnoj fazi u SFC
uslovima. Uticaj zapreminskog udela metanola (20-30 %), koncentracije amonijum-formijata
(15-25 mM) i temperature (20-30 °C) na vrednosti retencionih faktora (k) odabranih liganada
imidazolinskih i serotoninskih receptora je ispitana primenom centralnog kompozitnog
dizajna (Central Composite Design, CCD) na mixed-mode stacionarnoj fazi. Kao mobilna faza
korišćena je smeša superkritičnog CO2 i metanolnog rastvora amonijum-formijata uz dodatak
0,1% mravlje kiseline. Najznačajniji hromatografski faktori su izdvojeni step-wise postupkom
u višestrukoj linearnoj regresionoj analizi (Multiple Linear Regression, MLR), a njihova
statistička značajnost je procenjena primenom ANOVA testa. U konstruisanim retencionim
modelima, zapremina metanola i koncentracija pufera su pokazale najveći uticaj na retenciono
ponašanje testiranih jedinjenja (r > 0,90; p < 0,05), Slika 1. U koliko se teorijski predviđene
logk vrednosti uporede sa eksperimentalno dobijenim vrednostima na 35% i 15%
zapreminskim udelima metanola u mobilnoj fazi, uočava se da je prisutan visok stepen
slaganja (r > 0,98). Dobijeni rezultati potvrđuju uspešnu primenljivost metodologije
eksperimentalnog dizajna u cilju izvođenja minimalnog broja eksperimenata, prilikom
modelovanja i predikcije retencionog ponašanja liganda imidazolinskih i serotoninskih
receptora u SFC sistemima.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Modeling retention behaviour of imidazoline and serotonin receptor ligands under conditions of green SFC techique
T1  - Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora u uslovima ekološki bezbedne SFC tehnike
VL  - 71
IS  - 5 suplement
SP  - S126
EP  - S129
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4681
ER  - 

@conference{
author = "Obradović, Darija and Nikolaevich Stavrianidi, Andrey and Alekseevich Shpigun, Oleg and Agbaba, Danica",
year = "2021",
abstract = "A possibility of predicting retention behaviour without a large number of preliminary
experiments is a significant segment of theoretical and experimental investigations. By using
an appropriate design to define experimental conditions (Design of Experiments, DoE), the
retention behaviour of compounds can be described as a function of the most important
parameters of chromatographic system. Further, the DoE methodology has shown successful
applicability to modeling retention under the environmentally friendly Supercritical Fluid
Chromatography (SFC) conditions (1). In the last decades, robustness of the SFC instruments
has been improved in order to minimize ecological risks, and routine application of the SFC
technique has been introduced into many pharmaceutical strategies (e.g., the Good
Manufacturing Practice, GMP) (2). Therefore, the aim of our study was to define the influence
of the main chromatographic factors on the retention behaviour of fourteen imidazoline and
serotonin receptor ligands under the SFC conditions. Using the Central Composite Design
(CCD) approach, retention characteristics (k) of the test compounds were examined on the
mixed-mode stationary phase, with the mixture of supercritical CO2 and methanolic
ammonium-formate (with an addition of 0.1% formic acid) used as mobile phase. We took into
the consideration the influence of the following factors: volume fraction of methanol in mobile
phase (20-30 %), ammonium-formate concentration (15-25 mM), and temperature deviation
(20-30 °C). The most important chromatographic factors were selected by the step-wise
multilinear regression (MLR), and their statistical significance was assessed using the ANOVA
analysis. Based on the results obtained, it was established that the retention characteristics
were significantly influenced by changing the methanol and ammonium-formate
concentrations in mobile phase (r > 0.90, p < 0.05), Figure 1. High degree of agreement (r >
0.98) was observed, when the theoretically predicted logk values for 35% and 15% volume
fraction of methanol in mobile phase were compared with the experimental ones. The
obtained results confirm successful applicability of the experimental design methodology in
order to perform a minimum number of experiments, as demonstrated upon an example of
modeling and predicting the retention behaviour of imidazoline and serotonin receptor
ligands under the SFC conditions., Mogućnost predviđanja retencije u odsustvu velikog broja prethodnih eksperimenata,
značajan je segment teorijskih i eksperimentalnih ispitivanja. Odgovarajućim dizajnom
eksperimentalnih uslova (Design of Experiments, DoE), a na osnovu minimalnog broja
eksperimenata, može se definisati retenciono ponašanje jedinjenja u funkciji najznačajnijih
parametara hromatografskog sistema. Primena DoE metodologije je takođe zabeležena i
prilikom modelovanja retencije u uslovima ekološki bezbedne, superkritične fluidne
hromatografije (Supercritical Fluid Chromatography, SFC) (1). Zbog minimalnih ekoloških
rizika, robusnost SFC instrumenata je poboljšana, a rutinska primena SFC tehnike je uvedena
i u regulatorne farmaceutske propise (npr. dobra proizvođačka praksa; Good Manufacturing
Practice-GMP) (2). Na osnovu toga, cilj ovog istraživanja obuhvatio je definisanje uticaja
najznačajnijih faktora hromatografskog sistema na retenciono ponašanje 14 odabranih
liganada imidazolinskih i serotoninskih receptora na mixed-mode stacionarnoj fazi u SFC
uslovima. Uticaj zapreminskog udela metanola (20-30 %), koncentracije amonijum-formijata
(15-25 mM) i temperature (20-30 °C) na vrednosti retencionih faktora (k) odabranih liganada
imidazolinskih i serotoninskih receptora je ispitana primenom centralnog kompozitnog
dizajna (Central Composite Design, CCD) na mixed-mode stacionarnoj fazi. Kao mobilna faza
korišćena je smeša superkritičnog CO2 i metanolnog rastvora amonijum-formijata uz dodatak
0,1% mravlje kiseline. Najznačajniji hromatografski faktori su izdvojeni step-wise postupkom
u višestrukoj linearnoj regresionoj analizi (Multiple Linear Regression, MLR), a njihova
statistička značajnost je procenjena primenom ANOVA testa. U konstruisanim retencionim
modelima, zapremina metanola i koncentracija pufera su pokazale najveći uticaj na retenciono
ponašanje testiranih jedinjenja (r > 0,90; p < 0,05), Slika 1. U koliko se teorijski predviđene
logk vrednosti uporede sa eksperimentalno dobijenim vrednostima na 35% i 15%
zapreminskim udelima metanola u mobilnoj fazi, uočava se da je prisutan visok stepen
slaganja (r > 0,98). Dobijeni rezultati potvrđuju uspešnu primenljivost metodologije
eksperimentalnog dizajna u cilju izvođenja minimalnog broja eksperimenata, prilikom
modelovanja i predikcije retencionog ponašanja liganda imidazolinskih i serotoninskih
receptora u SFC sistemima.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Modeling retention behaviour of imidazoline and serotonin receptor ligands under conditions of green SFC techique, Modelovanje retencionog ponašanja liganada imidazolinskih i serotoninskih receptora u uslovima ekološki bezbedne SFC tehnike",
volume = "71",
number = "5 suplement",
pages = "S126-S129",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4681"
}

Obradović, D., Nikolaevich Stavrianidi, A., Alekseevich Shpigun, O.,& Agbaba, D.. (2021). Modeling retention behaviour of imidazoline and serotonin receptor ligands under conditions of green SFC techique. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 71(5 suplement), S126-S129.
https://hdl.handle.net/21.15107/rcub_farfar_4681

Obradović D, Nikolaevich Stavrianidi A, Alekseevich Shpigun O, Agbaba D. Modeling retention behaviour of imidazoline and serotonin receptor ligands under conditions of green SFC techique. in Arhiv za farmaciju. 2021;71(5 suplement):S126-S129.
https://hdl.handle.net/21.15107/rcub_farfar_4681 .

Obradović, Darija, Nikolaevich Stavrianidi, Andrey, Alekseevich Shpigun, Oleg, Agbaba, Danica, "Modeling retention behaviour of imidazoline and serotonin receptor ligands under conditions of green SFC techique" in Arhiv za farmaciju, 71, no. 5 suplement (2021):S126-S129,
https://hdl.handle.net/21.15107/rcub_farfar_4681 .

TY  - JOUR
AU  - Obradović, Darija
AU  - Komsta, Łukasz
AU  - Agbaba, Danica
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3558
AB  - The mixed-mode chromatographic behavior was estimated for imidazoline and serotonin receptor ligands, and their related compounds on dual hydrophilic/reversed phase stationary phase. The Box-Cox transfor- mation was used to obtain the most suitable mathematical equations which describe the mixed-mode retention. Optimal equations were found for the optimization parameter ( λ): λ= -1, λ= -0.5, λ= 0, λ= 0.5, and λ= 1. The proposed equations show satisfactory characteristics compared to standard mul- timodal and quadratic approaches. For a wide range of volume fractions of the mobile phase modifier, crossing between hydrophilic and reversed phase interactions (the turning point) was defined in terms of the minimal retention and the minimum value of the volume fraction of the aqueous eluent in the mobile phase. The cubic spline inter- polation was used as a reference method for estimation of the turning point. It was found out that the newly proposed equations can be used as alternative mathematical forms for the description of the dual retention mechanism and for the evaluation of the turning point. Three new experimental descriptors of the mixed-mode retention were proposed. Two descriptors quan- titatively characterize hydrophilic (log k H ) and reversed phase (log k R ) interactions, while the third one (log k A ) refers to the average retention for the whole HILIC/RP range. It was established that the main fac- tors which control dual nature of the mixed-mode retention are lipophilicity, dipol-dipol, van der Waals and hydrogen bonding interactions. It was concluded that the newly proposed estimations of the retention data reliably characterize the mixed-mode chromatographic behavior.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography
VL  - 1619
DO  - 10.1016/j.chroma.2020.460951
ER  - 

@article{
author = "Obradović, Darija and Komsta, Łukasz and Agbaba, Danica",
year = "2020",
abstract = "The mixed-mode chromatographic behavior was estimated for imidazoline and serotonin receptor ligands, and their related compounds on dual hydrophilic/reversed phase stationary phase. The Box-Cox transfor- mation was used to obtain the most suitable mathematical equations which describe the mixed-mode retention. Optimal equations were found for the optimization parameter ( λ): λ= -1, λ= -0.5, λ= 0, λ= 0.5, and λ= 1. The proposed equations show satisfactory characteristics compared to standard mul- timodal and quadratic approaches. For a wide range of volume fractions of the mobile phase modifier, crossing between hydrophilic and reversed phase interactions (the turning point) was defined in terms of the minimal retention and the minimum value of the volume fraction of the aqueous eluent in the mobile phase. The cubic spline inter- polation was used as a reference method for estimation of the turning point. It was found out that the newly proposed equations can be used as alternative mathematical forms for the description of the dual retention mechanism and for the evaluation of the turning point. Three new experimental descriptors of the mixed-mode retention were proposed. Two descriptors quan- titatively characterize hydrophilic (log k H ) and reversed phase (log k R ) interactions, while the third one (log k A ) refers to the average retention for the whole HILIC/RP range. It was established that the main fac- tors which control dual nature of the mixed-mode retention are lipophilicity, dipol-dipol, van der Waals and hydrogen bonding interactions. It was concluded that the newly proposed estimations of the retention data reliably characterize the mixed-mode chromatographic behavior.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography",
volume = "1619",
doi = "10.1016/j.chroma.2020.460951"
}

Obradović, D., Komsta, Ł.,& Agbaba, D.. (2020). Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography. in Journal of Chromatography A
Elsevier B.V.., 1619.
https://doi.org/10.1016/j.chroma.2020.460951

Obradović D, Komsta Ł, Agbaba D. Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography. in Journal of Chromatography A. 2020;1619.
doi:10.1016/j.chroma.2020.460951 .

Obradović, Darija, Komsta, Łukasz, Agbaba, Danica, "Novel computational approaches to retention modeling in dual hydrophilic interactions/reversed phase chromatography" in Journal of Chromatography A, 1619 (2020),
https://doi.org/10.1016/j.chroma.2020.460951 . .

TY  - CONF
AU  - Obradović, Darija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5156
AB  - Investigation of the retention behavior of a wide range of analytes (43 nitrogen containing heterocyclic
and guanidine derivatives such, as imidazoline and serotonin receptor ligands, or their related
compounds) was performed on the mixed-mode stationary phase in the combined
reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) modes. The imidazoline
receptor ligands are the imidazoline or guanidine analogues with numerous therapeutic applications
(such, as antihypertensives, diuretics, antiallergenics, antidiabetics, and antipsychotics), while the
serotonin receptor ligands are the piperazine derivatives which exert an effect on positive and negative
symptoms of schizophrenia, mania and mixed states of bipolar disorder.
On the mixed-mode stationary phase, the retention behaviour of investigated compounds
was described as a function of the aqueous eluent volume fractions, φ(aq), and total polarity of mobile
phase (Ptot). The turning point was discussed based on different mobile phase characteristics
representing the shift between the HILIC and the RP chromatographic mode. The influence
of molecular properties on the main retention characteristics (turining point and the extrapolated
retention parameters) is going to be discussed.
PB  - Institute of Chemistry University of Silesia in Katowice
C3  - 42nd Symposium Chromatographic Methods of Investigating Organic Compounds, Book of Abstracts
T1  - Investigation and prediction of retention characteristics of selected set of central nervous system active compounds on mixed-mode diol stationary phase
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5156
ER  - 

@conference{
author = "Obradović, Darija and Oljačić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2019",
abstract = "Investigation of the retention behavior of a wide range of analytes (43 nitrogen containing heterocyclic
and guanidine derivatives such, as imidazoline and serotonin receptor ligands, or their related
compounds) was performed on the mixed-mode stationary phase in the combined
reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) modes. The imidazoline
receptor ligands are the imidazoline or guanidine analogues with numerous therapeutic applications
(such, as antihypertensives, diuretics, antiallergenics, antidiabetics, and antipsychotics), while the
serotonin receptor ligands are the piperazine derivatives which exert an effect on positive and negative
symptoms of schizophrenia, mania and mixed states of bipolar disorder.
On the mixed-mode stationary phase, the retention behaviour of investigated compounds
was described as a function of the aqueous eluent volume fractions, φ(aq), and total polarity of mobile
phase (Ptot). The turning point was discussed based on different mobile phase characteristics
representing the shift between the HILIC and the RP chromatographic mode. The influence
of molecular properties on the main retention characteristics (turining point and the extrapolated
retention parameters) is going to be discussed.",
publisher = "Institute of Chemistry University of Silesia in Katowice",
journal = "42nd Symposium Chromatographic Methods of Investigating Organic Compounds, Book of Abstracts",
title = "Investigation and prediction of retention characteristics of selected set of central nervous system active compounds on mixed-mode diol stationary phase",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5156"
}

Obradović, D., Oljačić, S., Nikolić, K.,& Agbaba, D.. (2019). Investigation and prediction of retention characteristics of selected set of central nervous system active compounds on mixed-mode diol stationary phase. in 42nd Symposium Chromatographic Methods of Investigating Organic Compounds, Book of Abstracts
Institute of Chemistry University of Silesia in Katowice..
https://hdl.handle.net/21.15107/rcub_farfar_5156

Obradović D, Oljačić S, Nikolić K, Agbaba D. Investigation and prediction of retention characteristics of selected set of central nervous system active compounds on mixed-mode diol stationary phase. in 42nd Symposium Chromatographic Methods of Investigating Organic Compounds, Book of Abstracts. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_5156 .

Obradović, Darija, Oljačić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Investigation and prediction of retention characteristics of selected set of central nervous system active compounds on mixed-mode diol stationary phase" in 42nd Symposium Chromatographic Methods of Investigating Organic Compounds, Book of Abstracts (2019),
https://hdl.handle.net/21.15107/rcub_farfar_5156 .

TY  - JOUR
AU  - Obradović, Darija
AU  - Jovanović, Dušan
AU  - Pesić, Suncica
AU  - Tomić, Jovana
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3368
AB  - The retention behavior of ivabradine, its 11 related compounds, diltiazem and verapamil has been examined by thin-layer chromatography using non-polar stationary phase (RP-18) and the following mobile phases: methanol-6.25% aqueous ammonia, tetrahydrofuran - 6.25% aqueous ammonia, and also polar stationary phase (silica gel) with tetrahydrofuran - 6.25% methanolic ammonia as mobile phase. In the examined chromatographic systems, linear relationships were established between the retention coefficients, R-M(0) and m, and molecular properties of the investigated antiarrhythmic drugs. The Quantitative Structure Retention Relationship (QSRR) modeling was performed with use of the stepwise multiple linear regression, in order to select the most important molecular properties which influence the retention behavior. The developed models revealed that apart from lipophilicity also the molecular volume (V), and the hydrogen bond basicity (B) of the tested compounds are the most important for the retention behavior in the examined chromatographic systems.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Analysis of the retention behavior of selected antiarrhythmics by means of thin-layer chromatography
SP  - 1
EP  - 7
DO  - 10.1080/10826076.2019.1585613
ER  - 

@article{
author = "Obradović, Darija and Jovanović, Dušan and Pesić, Suncica and Tomić, Jovana and Oljačić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2019",
abstract = "The retention behavior of ivabradine, its 11 related compounds, diltiazem and verapamil has been examined by thin-layer chromatography using non-polar stationary phase (RP-18) and the following mobile phases: methanol-6.25% aqueous ammonia, tetrahydrofuran - 6.25% aqueous ammonia, and also polar stationary phase (silica gel) with tetrahydrofuran - 6.25% methanolic ammonia as mobile phase. In the examined chromatographic systems, linear relationships were established between the retention coefficients, R-M(0) and m, and molecular properties of the investigated antiarrhythmic drugs. The Quantitative Structure Retention Relationship (QSRR) modeling was performed with use of the stepwise multiple linear regression, in order to select the most important molecular properties which influence the retention behavior. The developed models revealed that apart from lipophilicity also the molecular volume (V), and the hydrogen bond basicity (B) of the tested compounds are the most important for the retention behavior in the examined chromatographic systems.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Analysis of the retention behavior of selected antiarrhythmics by means of thin-layer chromatography",
pages = "1-7",
doi = "10.1080/10826076.2019.1585613"
}

Obradović, D., Jovanović, D., Pesić, S., Tomić, J., Oljačić, S., Nikolić, K.,& Agbaba, D.. (2019). Analysis of the retention behavior of selected antiarrhythmics by means of thin-layer chromatography. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 1-7.
https://doi.org/10.1080/10826076.2019.1585613

Obradović D, Jovanović D, Pesić S, Tomić J, Oljačić S, Nikolić K, Agbaba D. Analysis of the retention behavior of selected antiarrhythmics by means of thin-layer chromatography. in Journal of Liquid Chromatography & Related Technologies. 2019;:1-7.
doi:10.1080/10826076.2019.1585613 .

Obradović, Darija, Jovanović, Dušan, Pesić, Suncica, Tomić, Jovana, Oljačić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Analysis of the retention behavior of selected antiarrhythmics by means of thin-layer chromatography" in Journal of Liquid Chromatography & Related Technologies (2019):1-7,
https://doi.org/10.1080/10826076.2019.1585613 . .

TY  - JOUR
AU  - Obradović, Darija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3332
AB  - Investigation of the retention behavior of a wide range of analytes, 43 nitrogen containing heterocyclic and guanidine derivatives such, as imidazoline and serotonin receptor ligands or their related compounds. was performed on mixed-mode stationary phase in the combined reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) modes. Suitability of the linear retention modelling in the HILIC and RP modes was tested including separate contributions from adsorption and partition. For the HILIC retention, the partition model was found to provide better description compared with the adsorption model. In a wider range of the aqueous eluent volume fractions, phi(aq), retention was described as a function of volume fractions and total polarity of mobile phase using the mixed-mode retention modelling. The obtained results revealed that the shift of the chromatographic mode can be calculated from the change of total polarity of mobile phase in a multimodal relation, logarithm of retention factor vs. total polarity, with the minimum value representing the turning point between the HILIC and the RP mode. Molecular properties of the investigated compounds that influence the retention behavior and the turning point were selected using Multiple Linear Regression (MLR) and Support Vector Machine (SVM). Slightly better statistical results were found for the logk(w)(RP)(aq)/MLR, logk(w)(HILIC) (org)/MLR, logk(b)(HILIC)(aq)/MLR, and phi(min) (aq)/SVM (RBF) QSRR models than for the logk(w)(RP)(aq)/SVM, logk(w)(NILIC)(org)/SVM, logk(b)(HILIC)(aq)/SVM. and phi(min)(aq)/MLR modelling. With this insight, it is possible to precisely define and predict the retention characteristics based on physicochemical properties of imidazoline and piperazine related compounds.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Investigation and prediction of retention characteristics of imidazoline and serotonin receptor ligands and their related compounds on mixed-mode stationary phase
VL  - 1585
SP  - 92
EP  - 104
DO  - 10.1016/j.chroma.2018.11.051
ER  - 

@article{
author = "Obradović, Darija and Oljačić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2019",
abstract = "Investigation of the retention behavior of a wide range of analytes, 43 nitrogen containing heterocyclic and guanidine derivatives such, as imidazoline and serotonin receptor ligands or their related compounds. was performed on mixed-mode stationary phase in the combined reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) modes. Suitability of the linear retention modelling in the HILIC and RP modes was tested including separate contributions from adsorption and partition. For the HILIC retention, the partition model was found to provide better description compared with the adsorption model. In a wider range of the aqueous eluent volume fractions, phi(aq), retention was described as a function of volume fractions and total polarity of mobile phase using the mixed-mode retention modelling. The obtained results revealed that the shift of the chromatographic mode can be calculated from the change of total polarity of mobile phase in a multimodal relation, logarithm of retention factor vs. total polarity, with the minimum value representing the turning point between the HILIC and the RP mode. Molecular properties of the investigated compounds that influence the retention behavior and the turning point were selected using Multiple Linear Regression (MLR) and Support Vector Machine (SVM). Slightly better statistical results were found for the logk(w)(RP)(aq)/MLR, logk(w)(HILIC) (org)/MLR, logk(b)(HILIC)(aq)/MLR, and phi(min) (aq)/SVM (RBF) QSRR models than for the logk(w)(RP)(aq)/SVM, logk(w)(NILIC)(org)/SVM, logk(b)(HILIC)(aq)/SVM. and phi(min)(aq)/MLR modelling. With this insight, it is possible to precisely define and predict the retention characteristics based on physicochemical properties of imidazoline and piperazine related compounds.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Investigation and prediction of retention characteristics of imidazoline and serotonin receptor ligands and their related compounds on mixed-mode stationary phase",
volume = "1585",
pages = "92-104",
doi = "10.1016/j.chroma.2018.11.051"
}

Obradović, D., Oljačić, S., Nikolić, K.,& Agbaba, D.. (2019). Investigation and prediction of retention characteristics of imidazoline and serotonin receptor ligands and their related compounds on mixed-mode stationary phase. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1585, 92-104.
https://doi.org/10.1016/j.chroma.2018.11.051

Obradović D, Oljačić S, Nikolić K, Agbaba D. Investigation and prediction of retention characteristics of imidazoline and serotonin receptor ligands and their related compounds on mixed-mode stationary phase. in Journal of Chromatography A. 2019;1585:92-104.
doi:10.1016/j.chroma.2018.11.051 .

Obradović, Darija, Oljačić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Investigation and prediction of retention characteristics of imidazoline and serotonin receptor ligands and their related compounds on mixed-mode stationary phase" in Journal of Chromatography A, 1585 (2019):92-104,
https://doi.org/10.1016/j.chroma.2018.11.051 . .

TY  - JOUR
AU  - Obradović, Darija
AU  - Stavrianidi, A.N
AU  - Ustinovich, K.B
AU  - Parenago, O.O
AU  - Shpigun, O.A
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3282
AB  - This work presents an investigation of retention characteristics of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction liquid chromatography (NA-HILIC) and supercritical fluid chromatography (SFC). The separation has been carried out by using methanol as a mobile phase modifier with addition of two types of additives (NH 4 HCOO; NH 4 HCOO/HCOOH) and two different stationary phases (diol; mixed-mode diol). The selectivity characteristics were observed based on S-factors, logk-logk plots and radar plots. NA-HILIC vs. SFC retention of tested compounds was also described by considering the molecular properties of the analytes within the LSER analysis. The differences between SFC vs. NA-HILIC retention of imidazoline and serotonin receptor ligands grow with the acid addition to a mobile phase, noticeably on mixed-mode diol stationary phase (S ≥ 87). In addition, the good selectivity performances of the certain NA-HILIC and SFC conditions were confirmed by good separation of structurally related compounds (α ≥ 2). The molecular basis of NA-HILIC and SFC retention were explained by using Abraham's equation. The dominant analyte descriptors influencing retention were hydrogen bonding and dipolar interactions. The current study will present the theory, and discuss the applicability within the SFC vs. NA-HILIC regimes. In this way, it was provided the placing of two relatively new methods (SFC, NA-HILIC) in the map of modern analytical chromatography in terms of the pharmaceutical analysis.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - The comparison of retention behaviour of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction chromatography and supercritical fluid chromatography
DO  - 10.1016/j.chroma.2019.04.054
ER  - 

@article{
author = "Obradović, Darija and Stavrianidi, A.N and Ustinovich, K.B and Parenago, O.O and Shpigun, O.A and Agbaba, Danica",
year = "2019",
abstract = "This work presents an investigation of retention characteristics of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction liquid chromatography (NA-HILIC) and supercritical fluid chromatography (SFC). The separation has been carried out by using methanol as a mobile phase modifier with addition of two types of additives (NH 4 HCOO; NH 4 HCOO/HCOOH) and two different stationary phases (diol; mixed-mode diol). The selectivity characteristics were observed based on S-factors, logk-logk plots and radar plots. NA-HILIC vs. SFC retention of tested compounds was also described by considering the molecular properties of the analytes within the LSER analysis. The differences between SFC vs. NA-HILIC retention of imidazoline and serotonin receptor ligands grow with the acid addition to a mobile phase, noticeably on mixed-mode diol stationary phase (S ≥ 87). In addition, the good selectivity performances of the certain NA-HILIC and SFC conditions were confirmed by good separation of structurally related compounds (α ≥ 2). The molecular basis of NA-HILIC and SFC retention were explained by using Abraham's equation. The dominant analyte descriptors influencing retention were hydrogen bonding and dipolar interactions. The current study will present the theory, and discuss the applicability within the SFC vs. NA-HILIC regimes. In this way, it was provided the placing of two relatively new methods (SFC, NA-HILIC) in the map of modern analytical chromatography in terms of the pharmaceutical analysis.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "The comparison of retention behaviour of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction chromatography and supercritical fluid chromatography",
doi = "10.1016/j.chroma.2019.04.054"
}

Obradović, D., Stavrianidi, A.N, Ustinovich, K.B, Parenago, O.O, Shpigun, O.A,& Agbaba, D.. (2019). The comparison of retention behaviour of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction chromatography and supercritical fluid chromatography. in Journal of Chromatography A
Elsevier B.V...
https://doi.org/10.1016/j.chroma.2019.04.054

Obradović D, Stavrianidi A, Ustinovich K, Parenago O, Shpigun O, Agbaba D. The comparison of retention behaviour of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction chromatography and supercritical fluid chromatography. in Journal of Chromatography A. 2019;.
doi:10.1016/j.chroma.2019.04.054 .

Obradović, Darija, Stavrianidi, A.N, Ustinovich, K.B, Parenago, O.O, Shpigun, O.A, Agbaba, Danica, "The comparison of retention behaviour of imidazoline and serotonin receptor ligands in non-aqueous hydrophilic interaction chromatography and supercritical fluid chromatography" in Journal of Chromatography A (2019),
https://doi.org/10.1016/j.chroma.2019.04.054 . .

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  - JOUR
AU  - Obradović, Darija
AU  - Andrić, Filip
AU  - Zlatović, Mario
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3036
AB  - Aripiprazole and ziprasidone are atypical antipsychotic drugs with the effect on positive and negative symptoms of schizophrenia, mania, and mixed states of bipolar disorder. Hansen's solubility parameters, (d), (p), and (h), which account for dispersive, polarizable, and hydrogen bonding contributions to the overall cohesive energy of a compound, are often used to assess pharmacokinetic properties of drugs. However, no data exist of solubility parameters for the drugs of interest in this study. Therefore, in the present study, partial least square regression (PLS), artificial neural networks (ANNs), regression trees (RT), boosted trees (BT), and random forests (RF) were applied to estimate Hansen's solubility parameters of ziprasidone, aripiprazole, and their impurities/metabolic derivatives, targeting their biopharmaceutical classes and absorption routes. A training set of 47 structurally diverse and pharmacologically active compounds and 290 molecular descriptors and pharmaceutically important properties were used to build the prediction models. The modeling approaches were compared by the sum of ranking differences, using the consensus values as a reference for the unknowns and the experimentally determined values as a gold standard for the calibration set. In both instances, the PLS models, together with ANNs, demonstrated better performance than RT, BT and especially RF. Based on the best scored models, we were able to pinpoint the most probable absorption sites for each drug and the corresponding metabolite, i.e., the upper parts of the gastrointestinal tract, small intestine, or absorption along entire length of gastrointestinal tract.
PB  - Wiley, Hoboken
T2  - Journal of Chemometrics
T1  - Modeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sites
VL  - 32
IS  - 4
DO  - 10.1002/cem.2996
ER  - 

@article{
author = "Obradović, Darija and Andrić, Filip and Zlatović, Mario and Agbaba, Danica",
year = "2018",
abstract = "Aripiprazole and ziprasidone are atypical antipsychotic drugs with the effect on positive and negative symptoms of schizophrenia, mania, and mixed states of bipolar disorder. Hansen's solubility parameters, (d), (p), and (h), which account for dispersive, polarizable, and hydrogen bonding contributions to the overall cohesive energy of a compound, are often used to assess pharmacokinetic properties of drugs. However, no data exist of solubility parameters for the drugs of interest in this study. Therefore, in the present study, partial least square regression (PLS), artificial neural networks (ANNs), regression trees (RT), boosted trees (BT), and random forests (RF) were applied to estimate Hansen's solubility parameters of ziprasidone, aripiprazole, and their impurities/metabolic derivatives, targeting their biopharmaceutical classes and absorption routes. A training set of 47 structurally diverse and pharmacologically active compounds and 290 molecular descriptors and pharmaceutically important properties were used to build the prediction models. The modeling approaches were compared by the sum of ranking differences, using the consensus values as a reference for the unknowns and the experimentally determined values as a gold standard for the calibration set. In both instances, the PLS models, together with ANNs, demonstrated better performance than RT, BT and especially RF. Based on the best scored models, we were able to pinpoint the most probable absorption sites for each drug and the corresponding metabolite, i.e., the upper parts of the gastrointestinal tract, small intestine, or absorption along entire length of gastrointestinal tract.",
publisher = "Wiley, Hoboken",
journal = "Journal of Chemometrics",
title = "Modeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sites",
volume = "32",
number = "4",
doi = "10.1002/cem.2996"
}

Obradović, D., Andrić, F., Zlatović, M.,& Agbaba, D.. (2018). Modeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sites. in Journal of Chemometrics
Wiley, Hoboken., 32(4).
https://doi.org/10.1002/cem.2996

Obradović D, Andrić F, Zlatović M, Agbaba D. Modeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sites. in Journal of Chemometrics. 2018;32(4).
doi:10.1002/cem.2996 .

Obradović, Darija, Andrić, Filip, Zlatović, Mario, Agbaba, Danica, "Modeling of Hansen's solubility parameters of aripiprazole, ziprasidone, and their impurities: A nonparametric comparison of models for prediction of drug absorption sites" in Journal of Chemometrics, 32, no. 4 (2018),
https://doi.org/10.1002/cem.2996 . .

TY  - CONF
AU  - Obradović, Darija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5167
AB  - Properties of solvents used for chromatography significantly influence retention behavior and separation of the analytes. Selection of an appropriate mobile phase mixture is based mainly on interactions of solvents with the analytes and stationary phase. ...
PB  - Institute of Chemistry University of Silesia in Katowice
C3  - 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
T1  - Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities
SP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5167
ER  - 

@conference{
author = "Obradović, Darija and Oljačić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2017",
abstract = "Properties of solvents used for chromatography significantly influence retention behavior and separation of the analytes. Selection of an appropriate mobile phase mixture is based mainly on interactions of solvents with the analytes and stationary phase. ...",
publisher = "Institute of Chemistry University of Silesia in Katowice",
journal = "40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts",
title = "Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities",
pages = "10",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5167"
}

Obradović, D., Oljačić, S., Nikolić, K.,& Agbaba, D.. (2017). Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
Institute of Chemistry University of Silesia in Katowice., 10.
https://hdl.handle.net/21.15107/rcub_farfar_5167

Obradović D, Oljačić S, Nikolić K, Agbaba D. Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts. 2017;:10.
https://hdl.handle.net/21.15107/rcub_farfar_5167 .

Obradović, Darija, Oljačić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities" in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts (2017):10,
https://hdl.handle.net/21.15107/rcub_farfar_5167 .

TY  - CONF
AU  - Oljačić, Slavica
AU  - Arsić, Anđela
AU  - Obradović, Darija
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5166
AB  - Retention behavior and lipophilicity of aripiprazole and its nine impurities as well as ziprasidone and its five impurities have been examined by thin layer chromatography using RP-18 stationary phase and different mixtures of methanol, water and ammonia; and ethanol, water and ammonia as mobile phases. ...
PB  - Institute of Chemistry University of Silesia in Katowice
C3  - 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
T1  - Analysis of retention behavior of selected antipsychotics and their impurities by thin layer chromatography
SP  - 3
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5166
ER  - 

@conference{
author = "Oljačić, Slavica and Arsić, Anđela and Obradović, Darija and Nikolić, Katarina and Agbaba, Danica",
year = "2017",
abstract = "Retention behavior and lipophilicity of aripiprazole and its nine impurities as well as ziprasidone and its five impurities have been examined by thin layer chromatography using RP-18 stationary phase and different mixtures of methanol, water and ammonia; and ethanol, water and ammonia as mobile phases. ...",
publisher = "Institute of Chemistry University of Silesia in Katowice",
journal = "40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts",
title = "Analysis of retention behavior of selected antipsychotics and their impurities by thin layer chromatography",
pages = "3",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5166"
}

Oljačić, S., Arsić, A., Obradović, D., Nikolić, K.,& Agbaba, D.. (2017). Analysis of retention behavior of selected antipsychotics and their impurities by thin layer chromatography. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
Institute of Chemistry University of Silesia in Katowice., 3.
https://hdl.handle.net/21.15107/rcub_farfar_5166

Oljačić S, Arsić A, Obradović D, Nikolić K, Agbaba D. Analysis of retention behavior of selected antipsychotics and their impurities by thin layer chromatography. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts. 2017;:3.
https://hdl.handle.net/21.15107/rcub_farfar_5166 .

Oljačić, Slavica, Arsić, Anđela, Obradović, Darija, Nikolić, Katarina, Agbaba, Danica, "Analysis of retention behavior of selected antipsychotics and their impurities by thin layer chromatography" in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts (2017):3,
https://hdl.handle.net/21.15107/rcub_farfar_5166 .

TY  - CONF
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Čarapić, Marija
AU  - Obradović, Darija
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5154
AB  - Demands to ensure safe and secure medicinal products for protection and treatment of
human health and society led to the development and implementation of numerous high
performance instrumental techniques for the estimation of their quality. ...
PB  - Institute of Chemistry University of Silesia in Katowice
C3  - 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
T1  - Possibilities of instrumental planar chromatography in drug analysis
SP  - 1
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5154
ER  - 

@conference{
author = "Oljačić, Slavica and Nikolić, Katarina and Čarapić, Marija and Obradović, Darija and Agbaba, Danica",
year = "2017",
abstract = "Demands to ensure safe and secure medicinal products for protection and treatment of
human health and society led to the development and implementation of numerous high
performance instrumental techniques for the estimation of their quality. ...",
publisher = "Institute of Chemistry University of Silesia in Katowice",
journal = "40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts",
title = "Possibilities of instrumental planar chromatography in drug analysis",
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Oljačić, S., Nikolić, K., Čarapić, M., Obradović, D.,& Agbaba, D.. (2017). Possibilities of instrumental planar chromatography in drug analysis. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts
Institute of Chemistry University of Silesia in Katowice., 1.
https://hdl.handle.net/21.15107/rcub_farfar_5154

Oljačić S, Nikolić K, Čarapić M, Obradović D, Agbaba D. Possibilities of instrumental planar chromatography in drug analysis. in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts. 2017;:1.
https://hdl.handle.net/21.15107/rcub_farfar_5154 .

Oljačić, Slavica, Nikolić, Katarina, Čarapić, Marija, Obradović, Darija, Agbaba, Danica, "Possibilities of instrumental planar chromatography in drug analysis" in 40th Symposium Chromatographic methods of investigating the organic compounds: Book of Abstracts (2017):1,
https://hdl.handle.net/21.15107/rcub_farfar_5154 .

TY  - JOUR
AU  - Obradović, Darija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3016
AB  - Influence of nine different solvents, either alone or in a mixture, on the retention behavior of ziprasidone and its five impurities were examined by normal-phase thin-layer chromatography. Migration distances of the examined compounds obtained under the examined chromatographic conditions were correlated with calculated mobile phase properties, such as Snyder polarity and Hansen solubility. Linear or second-order polynomial relationships with high correlation coefficients were established between investigated variables. The obtained mathematical functions and statistical results indicated that selected mobile phase properties can be used for the prediction of the retention behavior of ziprasidone and its five impurities. [GRAPHICS] .
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities
VL  - 40
IS  - 5-6
SP  - 247
EP  - 251
DO  - 10.1080/10826076.2017.1298026
ER  - 

@article{
author = "Obradović, Darija and Oljačić, Slavica and Nikolić, Katarina and Agbaba, Danica",
year = "2017",
abstract = "Influence of nine different solvents, either alone or in a mixture, on the retention behavior of ziprasidone and its five impurities were examined by normal-phase thin-layer chromatography. Migration distances of the examined compounds obtained under the examined chromatographic conditions were correlated with calculated mobile phase properties, such as Snyder polarity and Hansen solubility. Linear or second-order polynomial relationships with high correlation coefficients were established between investigated variables. The obtained mathematical functions and statistical results indicated that selected mobile phase properties can be used for the prediction of the retention behavior of ziprasidone and its five impurities. [GRAPHICS] .",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities",
volume = "40",
number = "5-6",
pages = "247-251",
doi = "10.1080/10826076.2017.1298026"
}

Obradović, D., Oljačić, S., Nikolić, K.,& Agbaba, D.. (2017). Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 40(5-6), 247-251.
https://doi.org/10.1080/10826076.2017.1298026

Obradović D, Oljačić S, Nikolić K, Agbaba D. Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities. in Journal of Liquid Chromatography & Related Technologies. 2017;40(5-6):247-251.
doi:10.1080/10826076.2017.1298026 .

Obradović, Darija, Oljačić, Slavica, Nikolić, Katarina, Agbaba, Danica, "Influence of selected mobile phase properties on the TLC retention behavior of ziprasidone and its impurities" in Journal of Liquid Chromatography & Related Technologies, 40, no. 5-6 (2017):247-251,
https://doi.org/10.1080/10826076.2017.1298026 . .