TY  - JOUR
AU  - Dokmanović, Jelena
AU  - Kasagić-Vujanović, Irena
AU  - Gagić, Žarko
AU  - Nikolić, Katarina
AU  - Čarapić, Marija
AU  - Agbaba, Danica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4474
AB  - Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5-methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min-1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15-35 μg mL-1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities
DO  - 10.1556/1326.2022.01111
ER  - 

@article{
author = "Dokmanović, Jelena and Kasagić-Vujanović, Irena and Gagić, Žarko and Nikolić, Katarina and Čarapić, Marija and Agbaba, Danica",
year = "2023",
abstract = "Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5-methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min-1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15-35 μg mL-1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities",
doi = "10.1556/1326.2022.01111"
}

Dokmanović, J., Kasagić-Vujanović, I., Gagić, Ž., Nikolić, K., Čarapić, M.,& Agbaba, D.. (2023). Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities. in Acta Chromatographica
Akademiai Kiado ZRt...
https://doi.org/10.1556/1326.2022.01111

Dokmanović J, Kasagić-Vujanović I, Gagić Ž, Nikolić K, Čarapić M, Agbaba D. Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities. in Acta Chromatographica. 2023;.
doi:10.1556/1326.2022.01111 .

Dokmanović, Jelena, Kasagić-Vujanović, Irena, Gagić, Žarko, Nikolić, Katarina, Čarapić, Marija, Agbaba, Danica, "Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities" in Acta Chromatographica (2023),
https://doi.org/10.1556/1326.2022.01111 . .

TY  - CONF
AU  - Čarapić, Marija
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4736
PB  - European Research Network on Signal Transduction CA18133
C3  - 6th ERNEST Meeting, Building a Comprehensive Map of GPCR Signal Transduction, 28-31 March, 2022.
T1  - Investigation of retention characteristics and an unknown degradant of ziprasidone, antipsychotic with unique profile binding for GPCRs receptor
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4736
ER  - 

@conference{
author = "Čarapić, Marija and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "6th ERNEST Meeting, Building a Comprehensive Map of GPCR Signal Transduction, 28-31 March, 2022.",
title = "Investigation of retention characteristics and an unknown degradant of ziprasidone, antipsychotic with unique profile binding for GPCRs receptor",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4736"
}

Čarapić, M., Nikolić, K.,& Agbaba, D.. (2022). Investigation of retention characteristics and an unknown degradant of ziprasidone, antipsychotic with unique profile binding for GPCRs receptor. in 6th ERNEST Meeting, Building a Comprehensive Map of GPCR Signal Transduction, 28-31 March, 2022.
European Research Network on Signal Transduction CA18133..
https://hdl.handle.net/21.15107/rcub_farfar_4736

Čarapić M, Nikolić K, Agbaba D. Investigation of retention characteristics and an unknown degradant of ziprasidone, antipsychotic with unique profile binding for GPCRs receptor. in 6th ERNEST Meeting, Building a Comprehensive Map of GPCR Signal Transduction, 28-31 March, 2022.. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4736 .

Čarapić, Marija, Nikolić, Katarina, Agbaba, Danica, "Investigation of retention characteristics and an unknown degradant of ziprasidone, antipsychotic with unique profile binding for GPCRs receptor" in 6th ERNEST Meeting, Building a Comprehensive Map of GPCR Signal Transduction, 28-31 March, 2022. (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4736 .

TY  - CONF
AU  - Čarapić, Marija
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://ernest-gpcr.eu/2nd-transatlantic-eci-gpcr-symposium-july-6-7-2022/
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4740
PB  - European Research Network on Signal Transduction CA18133
C3  - 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
T1  - The ANN-QSRR modeling of chromatographic properties of ziprasidone and its impurities
SP  - 48
EP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4740
ER  - 

@conference{
author = "Čarapić, Marija and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event",
title = "The ANN-QSRR modeling of chromatographic properties of ziprasidone and its impurities",
pages = "48-48",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4740"
}

Čarapić, M., Nikolić, K.,& Agbaba, D.. (2022). The ANN-QSRR modeling of chromatographic properties of ziprasidone and its impurities. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
European Research Network on Signal Transduction CA18133., 48-48.
https://hdl.handle.net/21.15107/rcub_farfar_4740

Čarapić M, Nikolić K, Agbaba D. The ANN-QSRR modeling of chromatographic properties of ziprasidone and its impurities. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event. 2022;:48-48.
https://hdl.handle.net/21.15107/rcub_farfar_4740 .

Čarapić, Marija, Nikolić, Katarina, Agbaba, Danica, "The ANN-QSRR modeling of chromatographic properties of ziprasidone and its impurities" in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event (2022):48-48,
https://hdl.handle.net/21.15107/rcub_farfar_4740 .

TY  - CONF
AU  - Čarapić, Marija
AU  - Marković, Bojan
AU  - Petković, Miloš
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://ernest-gpcr.eu/2nd-transatlantic-eci-gpcr-symposium-july-6-7-2022/
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4741
PB  - European Research Network on Signal Transduction CA18133
C3  - 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
T1  - Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS
SP  - 74
EP  - 74
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4741
ER  - 

@conference{
author = "Čarapić, Marija and Marković, Bojan and Petković, Miloš and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event",
title = "Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS",
pages = "74-74",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4741"
}

Čarapić, M., Marković, B., Petković, M., Nikolić, K.,& Agbaba, D.. (2022). Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event
European Research Network on Signal Transduction CA18133., 74-74.
https://hdl.handle.net/21.15107/rcub_farfar_4741

Čarapić M, Marković B, Petković M, Nikolić K, Agbaba D. Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS. in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event. 2022;:74-74.
https://hdl.handle.net/21.15107/rcub_farfar_4741 .

Čarapić, Marija, Marković, Bojan, Petković, Miloš, Nikolić, Katarina, Agbaba, Danica, "Characterisation of novel impurity of ziprasidone with NMR spectroscopy and UPLC-MS/MS" in 2nd Transatlantic ECI GPCR Symposium - Early Career Investigators – July 6-7, 2022, Online event (2022):74-74,
https://hdl.handle.net/21.15107/rcub_farfar_4741 .

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

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

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

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

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

TY  - CONF
AU  - Čarapić, Marija
AU  - Vojvodić, Ljiljana
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4601
AB  - Guideline ICHQ2(R1) (June 1995) provides general recommendations about
performing the validation of standard analytical procedures (HPLC/TLC/GC) used for testing
the active substance (AS)/finished product in order to show that the method is suitable for
its intended use (ensuring the quality of the medicine). The development of a new guideline
ICHQ14 Analytical procedure development is underway, which consequently led to a revision
of the guideline ICHQ2 in the R2 version (comments until July 2022). The aim of this paper is
to present an overview of new regulatory elements that should be considered during the
validation of the analytical procedure. In relation to R1, ICHQ2(R2) provides
recommendations for performing/evaluating various validation tests taking into account the
specificity of each analytical procedure. Validation principles covering the use of
spectroscopic/spectrometric data (e.g. NIR/Raman/NMR/MS) are described, some of which
often require multivariate statistical analyzes. Guideline-R1 referred to the most frequently
tested specification/process parameters (identification, testing of impurities
quantitatively/limit test, assay (1,2)). R2 describes the methodology for performing
validation for testing: elemental impurities (ICP-OES/ICP-MS), genotoxic impurities (LC/MS),
dissolution testing (HPLC), particle size determination, core tablet assay by NIR (e.g. in
continuous manufacturing), quantitative 1 H-NMR for the assay of AS. The validation
methodology used in specific tests for biological/biotechnological drugs for biological assay
(ELISA, SPR) and impurity testing-quantitative PCR, is also described. If scientifically
justified, relevant data from development studies (ICHQ14) can be used instead of validation
or the validation process can be abbreviated when an already established platform analytical
procedure is used for a new purpose.
AB  - Smernica ICHQ2(R1) (jun 1995.) daje opšte preporuke o načinu izvođenja validacije
standardnih analitičkih metoda (HPLC/TLC/GC) koje se koriste za ispitivanje aktivne
supstance (AS) i gotovog proizvoda što ima za cilj da pokaže da je metoda pogodna za
predviđenu svrhu (obezbeđenje kvaliteta leka). U toku je razvoj nove smernice ICHQ14 o
razvoju analitičkih metoda što je posledično dovelo do revizije smernice ICHQ2 u verziju R2
(na javnoj raspravi do jula 2022.). Cilj ovog rada je da se prikaže pregled novih regulatornih
elemenata koje treba razmatrati u toku validacije analitičke procedure. U odnosu na R1,
ICHQ2(R2) daje preporuke za izvođenje i procenu različitih testova validacije uzimajući u
obzir specifičnost svake analitičke procedure. Biće opisani postupci validacije koji pokrivaju
upotrebu spektroskopskih/spektrometrijskih podataka (npr. NIR, Raman, NMR ili MS) od
kojih neki često zahtevaju multivarijantne statističke analize. Smernica-R1 se odnosila na
najčešće ispitivane specifikacijske/procesne parametre (identifikacija, ispitivanje nečistoća
kvantitativno/limit test, sadržaj AS (1,2)). Verzija R2 opisuje metodologiju izvođenja
validacije za ispitivanje elelmentalnih nečistoća (ICP-OES/ICP-MS), ispitivanje genotoksičnih
nečistoća - LC/MS, ispitivanja brzine oslobađanja aktivne supstance-HPLC, određivanje
veličine čestica, validacija NIR metode za ispitivanje sadržaja AS u tabletnom jezgru (npr. kod
kontinuirane proizvodnje), validacija H-NMR za određivanje sadržaja AS. Opisana je i
validaciona metodologija koja se primenjuje kod spefičnih testova za biološke/biotehnološke
lekove za određivanje sadržaja AS (ELISA, SPR) i ispitivanje nečistoća-PCR. Ako je to
naučno opravdano, odgovarajući podaci dobijeni iz razvojnih studija (ICHQ14)
mogu se koristiti umesto validacije ili postupak validacije može biti skraćen kada
se već utvrđena platforma analitičke procedure koristi u novu svrhu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - New regulatory requirements in revision of ICH Q2(R2) guideline on the validation of analytical procedures
T1  - Novi regulatorni zahtevi u reviziji ICH Q2 smernice o validaciji analitičkih metoda
VL  - 72
IS  - 4 suplement
SP  - S538
EP  - S539
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4601
ER  - 

@conference{
author = "Čarapić, Marija and Vojvodić, Ljiljana and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
abstract = "Guideline ICHQ2(R1) (June 1995) provides general recommendations about
performing the validation of standard analytical procedures (HPLC/TLC/GC) used for testing
the active substance (AS)/finished product in order to show that the method is suitable for
its intended use (ensuring the quality of the medicine). The development of a new guideline
ICHQ14 Analytical procedure development is underway, which consequently led to a revision
of the guideline ICHQ2 in the R2 version (comments until July 2022). The aim of this paper is
to present an overview of new regulatory elements that should be considered during the
validation of the analytical procedure. In relation to R1, ICHQ2(R2) provides
recommendations for performing/evaluating various validation tests taking into account the
specificity of each analytical procedure. Validation principles covering the use of
spectroscopic/spectrometric data (e.g. NIR/Raman/NMR/MS) are described, some of which
often require multivariate statistical analyzes. Guideline-R1 referred to the most frequently
tested specification/process parameters (identification, testing of impurities
quantitatively/limit test, assay (1,2)). R2 describes the methodology for performing
validation for testing: elemental impurities (ICP-OES/ICP-MS), genotoxic impurities (LC/MS),
dissolution testing (HPLC), particle size determination, core tablet assay by NIR (e.g. in
continuous manufacturing), quantitative 1 H-NMR for the assay of AS. The validation
methodology used in specific tests for biological/biotechnological drugs for biological assay
(ELISA, SPR) and impurity testing-quantitative PCR, is also described. If scientifically
justified, relevant data from development studies (ICHQ14) can be used instead of validation
or the validation process can be abbreviated when an already established platform analytical
procedure is used for a new purpose., Smernica ICHQ2(R1) (jun 1995.) daje opšte preporuke o načinu izvođenja validacije
standardnih analitičkih metoda (HPLC/TLC/GC) koje se koriste za ispitivanje aktivne
supstance (AS) i gotovog proizvoda što ima za cilj da pokaže da je metoda pogodna za
predviđenu svrhu (obezbeđenje kvaliteta leka). U toku je razvoj nove smernice ICHQ14 o
razvoju analitičkih metoda što je posledično dovelo do revizije smernice ICHQ2 u verziju R2
(na javnoj raspravi do jula 2022.). Cilj ovog rada je da se prikaže pregled novih regulatornih
elemenata koje treba razmatrati u toku validacije analitičke procedure. U odnosu na R1,
ICHQ2(R2) daje preporuke za izvođenje i procenu različitih testova validacije uzimajući u
obzir specifičnost svake analitičke procedure. Biće opisani postupci validacije koji pokrivaju
upotrebu spektroskopskih/spektrometrijskih podataka (npr. NIR, Raman, NMR ili MS) od
kojih neki često zahtevaju multivarijantne statističke analize. Smernica-R1 se odnosila na
najčešće ispitivane specifikacijske/procesne parametre (identifikacija, ispitivanje nečistoća
kvantitativno/limit test, sadržaj AS (1,2)). Verzija R2 opisuje metodologiju izvođenja
validacije za ispitivanje elelmentalnih nečistoća (ICP-OES/ICP-MS), ispitivanje genotoksičnih
nečistoća - LC/MS, ispitivanja brzine oslobađanja aktivne supstance-HPLC, određivanje
veličine čestica, validacija NIR metode za ispitivanje sadržaja AS u tabletnom jezgru (npr. kod
kontinuirane proizvodnje), validacija H-NMR za određivanje sadržaja AS. Opisana je i
validaciona metodologija koja se primenjuje kod spefičnih testova za biološke/biotehnološke
lekove za određivanje sadržaja AS (ELISA, SPR) i ispitivanje nečistoća-PCR. Ako je to
naučno opravdano, odgovarajući podaci dobijeni iz razvojnih studija (ICHQ14)
mogu se koristiti umesto validacije ili postupak validacije može biti skraćen kada
se već utvrđena platforma analitičke procedure koristi u novu svrhu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "New regulatory requirements in revision of ICH Q2(R2) guideline on the validation of analytical procedures, Novi regulatorni zahtevi u reviziji ICH Q2 smernice o validaciji analitičkih metoda",
volume = "72",
number = "4 suplement",
pages = "S538-S539",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4601"
}

Čarapić, M., Vojvodić, L., Nikolić, K.,& Agbaba, D.. (2022). New regulatory requirements in revision of ICH Q2(R2) guideline on the validation of analytical procedures. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S538-S539.
https://hdl.handle.net/21.15107/rcub_farfar_4601

Čarapić M, Vojvodić L, Nikolić K, Agbaba D. New regulatory requirements in revision of ICH Q2(R2) guideline on the validation of analytical procedures. in Arhiv za farmaciju. 2022;72(4 suplement):S538-S539.
https://hdl.handle.net/21.15107/rcub_farfar_4601 .

Čarapić, Marija, Vojvodić, Ljiljana, Nikolić, Katarina, Agbaba, Danica, "New regulatory requirements in revision of ICH Q2(R2) guideline on the validation of analytical procedures" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S538-S539,
https://hdl.handle.net/21.15107/rcub_farfar_4601 .

TY  - CONF
AU  - Čarapić, Marija
AU  - Marković, Bojan
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4600
AB  - Ziprasidone, bensiothiasol piperazynylindolone derivative is second generation
antipsychotic drug used for the treatment of schizophrenia and in acute maniac/mixed
episodes associated with bipolar disorder. It has unique G-protein coupled receptor binding
profile with relatively low propensity for weight gain (1). Recently, it became an official
active pharmaceutical ingredient in European Pharmacopoeia, where there are three official
chromatographic systems, one for the assay and two other for early-eluiting and late-eluting
impurities. Therefore, the purpose of this investigation was to develop and validate a fast,
highly sensitive UHPLC-MS/MS method for the analysis of ziprasidone and its five impurities,
significantly differing in polarity and pKa. Separation was performed using Thermo ACCELA
UHPLC system (Thermo Scientific, Waltham, MA, USA) equipped with triple quad Mass
Spectrometer Thermo TSQ Quantum Access Max (Thermo Scientific, Waltham, MA, USA)
with a heated electro-spray ionization interface. Satisfactory chromatographic separation
was achieved using a gradient elution with mobile phase A (10mM ammonium formate
buffer, pH 4.7) and mobile phase B (acetonitrile) on a Acquity UPLC BEH C18 (50×2.1 mm,
1.7 μm) column with mobile phase flow rate of 300 μL/min. Sample injection volume was 10
μL. The analysis runtime was 7 minutes. The method was validated according to the
International Conference of Harmonization (ICH) guidelines and validation included
parameters such as specificity, linearity, accuracy, precision, limit of quantification and limit
of detection. The proposed rapid and sensitive method is convenient and reliable for the
assay and purity control in raw materials and in dosage forms (2).
AB  - Ziprasidon, derivat benzizotiazol piperazinilindolona, je antipsihotik druge generacije
koji se koristi za lečenje šizofrenije, kod akutnih maničnih ili mešovitih epizoda povezanih sa
bipolarnim poremećajem. Ima jedinstveni profil vezivanja za G protein-spregnute receptore
(GPCR) i relativno retko neželjeno dejstvo povećanja telesne težine (1). Nedavno je
monografija dve soli ziprasidona postala oficinalna u Evropskoj farmakopeji u kojoj se
ispitivanje vrši pomoću tri hromatografska sistema: ispitivanje sadržaja i dva odvojena
sistema za više i manje polarne nečistoće. Svrha ovog istraživanja bila da se razvije i validira
brza i visoko osetljiva UHPLC-MS/MS metoda za istovremeno ispitivanje ziprasidona i
njegovih pet nečistoća, koje se značajno razlikuju po polarnosti i pKa. Hromatografska
analiza je vršena na Thermo ACCELA UHPLC sistemu koji je spregnut sa tripl kvadrupolskim
masenim analizatorom Thermo TSQ Quantum Access Max (Thermo Scientific, Valtham, MA,
USA) sa elektrosprej jonizacijom na povišenoj temperaturi (HESI) kao jonskim izvorom.
Zadovoljavajuće razdvajanje dobijeno je korišć enjem gradijentog eluiranja sa mobilnom
fazom A (10 mM amonijum-formijat, pH 4,7) i mobilnom fazom B (acetonitril) na Acquity
UPLC BEH 50×2,1 mm, 1,7 μm (Waters) stacionarnoj fazi na temperaturi od 30ºC i pri
protoku mobilne faze od 300 μL/min. Zapremina injektovanja ispitivanih rastvora bila je
10 μL. Trajanje analize je 7 minuta (2). Metoda je validirana u skladu sa ICH (International
Council for Harmonisation) smernicom i pokazana je specifičnost metode, linearnost,
tačnost, preciznost, limit kvantifikacije i limit detekcije. Potvrđeno je da se brza i osetljiva
UHPLC-MS/MS metoda može primeniti za ispitivanje ziprasidona i njegovih nečistoća u
aktivnoj supstanci i doziranim oblicima.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities
T1  - Razvoj i validacija UHPLC‐MS/MS metode za ispitivanje ziprasidona i njegovih nečistoća
VL  - 72
IS  - 4 suplement
SP  - S536
EP  - S537
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4600
ER  - 

@conference{
author = "Čarapić, Marija and Marković, Bojan and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
abstract = "Ziprasidone, bensiothiasol piperazynylindolone derivative is second generation
antipsychotic drug used for the treatment of schizophrenia and in acute maniac/mixed
episodes associated with bipolar disorder. It has unique G-protein coupled receptor binding
profile with relatively low propensity for weight gain (1). Recently, it became an official
active pharmaceutical ingredient in European Pharmacopoeia, where there are three official
chromatographic systems, one for the assay and two other for early-eluiting and late-eluting
impurities. Therefore, the purpose of this investigation was to develop and validate a fast,
highly sensitive UHPLC-MS/MS method for the analysis of ziprasidone and its five impurities,
significantly differing in polarity and pKa. Separation was performed using Thermo ACCELA
UHPLC system (Thermo Scientific, Waltham, MA, USA) equipped with triple quad Mass
Spectrometer Thermo TSQ Quantum Access Max (Thermo Scientific, Waltham, MA, USA)
with a heated electro-spray ionization interface. Satisfactory chromatographic separation
was achieved using a gradient elution with mobile phase A (10mM ammonium formate
buffer, pH 4.7) and mobile phase B (acetonitrile) on a Acquity UPLC BEH C18 (50×2.1 mm,
1.7 μm) column with mobile phase flow rate of 300 μL/min. Sample injection volume was 10
μL. The analysis runtime was 7 minutes. The method was validated according to the
International Conference of Harmonization (ICH) guidelines and validation included
parameters such as specificity, linearity, accuracy, precision, limit of quantification and limit
of detection. The proposed rapid and sensitive method is convenient and reliable for the
assay and purity control in raw materials and in dosage forms (2)., Ziprasidon, derivat benzizotiazol piperazinilindolona, je antipsihotik druge generacije
koji se koristi za lečenje šizofrenije, kod akutnih maničnih ili mešovitih epizoda povezanih sa
bipolarnim poremećajem. Ima jedinstveni profil vezivanja za G protein-spregnute receptore
(GPCR) i relativno retko neželjeno dejstvo povećanja telesne težine (1). Nedavno je
monografija dve soli ziprasidona postala oficinalna u Evropskoj farmakopeji u kojoj se
ispitivanje vrši pomoću tri hromatografska sistema: ispitivanje sadržaja i dva odvojena
sistema za više i manje polarne nečistoće. Svrha ovog istraživanja bila da se razvije i validira
brza i visoko osetljiva UHPLC-MS/MS metoda za istovremeno ispitivanje ziprasidona i
njegovih pet nečistoća, koje se značajno razlikuju po polarnosti i pKa. Hromatografska
analiza je vršena na Thermo ACCELA UHPLC sistemu koji je spregnut sa tripl kvadrupolskim
masenim analizatorom Thermo TSQ Quantum Access Max (Thermo Scientific, Valtham, MA,
USA) sa elektrosprej jonizacijom na povišenoj temperaturi (HESI) kao jonskim izvorom.
Zadovoljavajuće razdvajanje dobijeno je korišć enjem gradijentog eluiranja sa mobilnom
fazom A (10 mM amonijum-formijat, pH 4,7) i mobilnom fazom B (acetonitril) na Acquity
UPLC BEH 50×2,1 mm, 1,7 μm (Waters) stacionarnoj fazi na temperaturi od 30ºC i pri
protoku mobilne faze od 300 μL/min. Zapremina injektovanja ispitivanih rastvora bila je
10 μL. Trajanje analize je 7 minuta (2). Metoda je validirana u skladu sa ICH (International
Council for Harmonisation) smernicom i pokazana je specifičnost metode, linearnost,
tačnost, preciznost, limit kvantifikacije i limit detekcije. Potvrđeno je da se brza i osetljiva
UHPLC-MS/MS metoda može primeniti za ispitivanje ziprasidona i njegovih nečistoća u
aktivnoj supstanci i doziranim oblicima.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities, Razvoj i validacija UHPLC‐MS/MS metode za ispitivanje ziprasidona i njegovih nečistoća",
volume = "72",
number = "4 suplement",
pages = "S536-S537",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4600"
}

Čarapić, M., Marković, B., Nikolić, K.,& Agbaba, D.. (2022). Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S536-S537.
https://hdl.handle.net/21.15107/rcub_farfar_4600

Čarapić M, Marković B, Nikolić K, Agbaba D. Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities. in Arhiv za farmaciju. 2022;72(4 suplement):S536-S537.
https://hdl.handle.net/21.15107/rcub_farfar_4600 .

Čarapić, Marija, Marković, Bojan, Nikolić, Katarina, Agbaba, Danica, "Development and validation of UHPLC-MS/MS method for analysis of ziprasidone and its impurities" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S536-S537,
https://hdl.handle.net/21.15107/rcub_farfar_4600 .

TY  - CONF
AU  - Čarapić, Marija
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4476
AB  - Most chemical syntheses use highly reactive molecules, which are often DNA-reactive
(mutagens). They may be present in the active substance (AS) or in the drug product as
genotoxic impurities (GI). The mechanism of action of most GIs is based on DNA modification
by direct binding (electrophilic - alkylating agents), insertion into the DNA chain
(topoisomerase inhibitors) and antimetabolites (purine/pyrimidine analogs). Structural
alerts (SA) for carcinogenic activity are defined as functional groups or substructures of
compounds associated with carcinogenic activity (1). SA indicates a chemical group that causes
toxic effects through one or several common mechanisms of action. GIs can bind directly to DNA
or after metabolic transformations (oxidation and reduction), thus the SA structure may indicate
the formation of several toxic metabolites. The risk assessment for the presence of GIs is a
mandatory part in the module 3 (AS/DP impurity profile) submitted in the marketing authorization
procedure, also in the approval of clinical trials. Guideline ICHM7(2) provides recommendations
for identification, categorization, qualification and control strategy of mutagenic impurities in
order to limit the potential carcinogenic risk. According to ICHM7, the classification (class 1-5) of
all impurities is performed on the basis of data on carcinogenicity and bacterial mutagenicity (BM)
from databases/scientific literature. If data are not available, computational toxicological
assessment (QSAR) is performed and BM is predicted with two independent models. If any of
model shows SA structures, a BM assay (Ames test) is performed. The high potent mutagenic
carcinogens (aflatoxins, nitrosamines, alkyl-azoxy compounds) referred to as “cohort of concern”.
AB  - U većini hemijskih sinteza se koriste veoma reaktivni molekuli koji su često i DNK –
reaktivni (mutageni). Oni mogu biti prisutni u aktivnoj supstanci (AS) ili gotovom proizvodu
(GP) kao genotoksične nečistoće (GN). Mehanizam dejstva većine GN se zasniva na
modifikaciji DNK i to direktnim vezivanjem (elektrofili - alkilujući agensi), umetanjem u
lanac DNK (inhibitori topoizomeraze) i antimetaboliti (purinski/pirimidinski analozi).
Upozoravajuće strukture (SA) za kancerogenu aktivnost se definišu kao funkcionalne grupe
ili delovi strukture jedinjenja koje su povezane sa kancerogenom aktivnošću (1). SA ukazuje
na hemijsku grupu jedinjenja koja izaziva toksične efekte kroz jedan ili nekoliko obično
zajedničkih mehanizama delovanja. GN mogu direktno da se vezuju za DNK ili nakon
metaboličkih transformacija (oksidacija i redukcija) pa SA struktura može da ukaže na
nastanak nekoliko toksičnih metabolita. Procena rizika na prisustvo GN u delu koji se odnosi
na profil nečistoća AS/GP je obavezan deo dokumentacije o kvalitetu leka koji se podnosi u
postupku registracije leka, kao i odobravanja kliničkih ispitivanja. U smernici ICHM7(2) su
date preporuke za identifikaciju, kategorizaciju, kvalifikaciju i kontrolnu strategiju
mutagenih nečistoća kako bi se ograničio potencijalni kancerogeni rizik. Prema ICHM7 se
vrši klasifikacija (klase 1-5) svih nečistoća na osnovu podataka o kancerogenosti i
bakterijskoj mutagenosti iz baza i naučne literature. Ako podaci nisu dostupni sprovodi se in
silico toksikološka procena (QSAR) i predviđa se bakterijska mutagenost sa dva nezavisna
modela. Ako jedan od modela pokaže SA strukture, radi se test povratne mutacije na
bakterijama (Ames test). Posebno se razmatraju visoko potentni mutageni kancerogeni
(aflatoksini, nitrozamini, alkil-azoksi jedinjenja).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Genotoxic impurities in medicinal products – regulatory requirements
T1  - Genotoksične nečistoće u lekovima ‐ regulatorni zahtevi
VL  - 72
IS  - 4 suplement
SP  - S133
EP  - S134
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4476
ER  - 

@conference{
author = "Čarapić, Marija and Nikolić, Katarina and Agbaba, Danica",
year = "2022",
abstract = "Most chemical syntheses use highly reactive molecules, which are often DNA-reactive
(mutagens). They may be present in the active substance (AS) or in the drug product as
genotoxic impurities (GI). The mechanism of action of most GIs is based on DNA modification
by direct binding (electrophilic - alkylating agents), insertion into the DNA chain
(topoisomerase inhibitors) and antimetabolites (purine/pyrimidine analogs). Structural
alerts (SA) for carcinogenic activity are defined as functional groups or substructures of
compounds associated with carcinogenic activity (1). SA indicates a chemical group that causes
toxic effects through one or several common mechanisms of action. GIs can bind directly to DNA
or after metabolic transformations (oxidation and reduction), thus the SA structure may indicate
the formation of several toxic metabolites. The risk assessment for the presence of GIs is a
mandatory part in the module 3 (AS/DP impurity profile) submitted in the marketing authorization
procedure, also in the approval of clinical trials. Guideline ICHM7(2) provides recommendations
for identification, categorization, qualification and control strategy of mutagenic impurities in
order to limit the potential carcinogenic risk. According to ICHM7, the classification (class 1-5) of
all impurities is performed on the basis of data on carcinogenicity and bacterial mutagenicity (BM)
from databases/scientific literature. If data are not available, computational toxicological
assessment (QSAR) is performed and BM is predicted with two independent models. If any of
model shows SA structures, a BM assay (Ames test) is performed. The high potent mutagenic
carcinogens (aflatoxins, nitrosamines, alkyl-azoxy compounds) referred to as “cohort of concern”., U većini hemijskih sinteza se koriste veoma reaktivni molekuli koji su često i DNK –
reaktivni (mutageni). Oni mogu biti prisutni u aktivnoj supstanci (AS) ili gotovom proizvodu
(GP) kao genotoksične nečistoće (GN). Mehanizam dejstva većine GN se zasniva na
modifikaciji DNK i to direktnim vezivanjem (elektrofili - alkilujući agensi), umetanjem u
lanac DNK (inhibitori topoizomeraze) i antimetaboliti (purinski/pirimidinski analozi).
Upozoravajuće strukture (SA) za kancerogenu aktivnost se definišu kao funkcionalne grupe
ili delovi strukture jedinjenja koje su povezane sa kancerogenom aktivnošću (1). SA ukazuje
na hemijsku grupu jedinjenja koja izaziva toksične efekte kroz jedan ili nekoliko obično
zajedničkih mehanizama delovanja. GN mogu direktno da se vezuju za DNK ili nakon
metaboličkih transformacija (oksidacija i redukcija) pa SA struktura može da ukaže na
nastanak nekoliko toksičnih metabolita. Procena rizika na prisustvo GN u delu koji se odnosi
na profil nečistoća AS/GP je obavezan deo dokumentacije o kvalitetu leka koji se podnosi u
postupku registracije leka, kao i odobravanja kliničkih ispitivanja. U smernici ICHM7(2) su
date preporuke za identifikaciju, kategorizaciju, kvalifikaciju i kontrolnu strategiju
mutagenih nečistoća kako bi se ograničio potencijalni kancerogeni rizik. Prema ICHM7 se
vrši klasifikacija (klase 1-5) svih nečistoća na osnovu podataka o kancerogenosti i
bakterijskoj mutagenosti iz baza i naučne literature. Ako podaci nisu dostupni sprovodi se in
silico toksikološka procena (QSAR) i predviđa se bakterijska mutagenost sa dva nezavisna
modela. Ako jedan od modela pokaže SA strukture, radi se test povratne mutacije na
bakterijama (Ames test). Posebno se razmatraju visoko potentni mutageni kancerogeni
(aflatoksini, nitrozamini, alkil-azoksi jedinjenja).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Genotoxic impurities in medicinal products – regulatory requirements, Genotoksične nečistoće u lekovima ‐ regulatorni zahtevi",
volume = "72",
number = "4 suplement",
pages = "S133-S134",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4476"
}

Čarapić, M., Nikolić, K.,& Agbaba, D.. (2022). Genotoxic impurities in medicinal products – regulatory requirements. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S133-S134.
https://hdl.handle.net/21.15107/rcub_farfar_4476

Čarapić M, Nikolić K, Agbaba D. Genotoxic impurities in medicinal products – regulatory requirements. in Arhiv za farmaciju. 2022;72(4 suplement):S133-S134.
https://hdl.handle.net/21.15107/rcub_farfar_4476 .

Čarapić, Marija, Nikolić, Katarina, Agbaba, Danica, "Genotoxic impurities in medicinal products – regulatory requirements" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S133-S134,
https://hdl.handle.net/21.15107/rcub_farfar_4476 .

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

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

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

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

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

TY  - JOUR
AU  - 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  - 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  - JOUR
AU  - Ružić, Dušan
AU  - Petković, Miloš
AU  - Agbaba, Danica
AU  - Ganesan, A.
AU  - Nikolić, Katarina
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3369
AB  - Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Molecular Informatics
T1  - Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors
VL  - 38
IS  - 5
DO  - 10.1002/minf.201800083
ER  - 

@article{
author = "Ružić, Dušan and Petković, Miloš and Agbaba, Danica and Ganesan, A. and Nikolić, Katarina",
year = "2019",
abstract = "Histone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Molecular Informatics",
title = "Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors",
volume = "38",
number = "5",
doi = "10.1002/minf.201800083"
}

Ružić, D., Petković, M., Agbaba, D., Ganesan, A.,& Nikolić, K.. (2019). Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors. in Molecular Informatics
Wiley-VCH Verlag GMBH, Weinheim., 38(5).
https://doi.org/10.1002/minf.201800083

Ružić D, Petković M, Agbaba D, Ganesan A, Nikolić K. Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors. in Molecular Informatics. 2019;38(5).
doi:10.1002/minf.201800083 .

Ružić, Dušan, Petković, Miloš, Agbaba, Danica, Ganesan, A., Nikolić, Katarina, "Combined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitors" in Molecular Informatics, 38, no. 5 (2019),
https://doi.org/10.1002/minf.201800083 . .

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  - Bouchet, Samuel
AU  - Linot, Camille
AU  - Ružić, Dušan
AU  - Agbaba, Danica
AU  - Fouchaq, Benoit
AU  - Roche, Joelle
AU  - Nikolić, Katarina
AU  - Blanquart, Christophe
AU  - Bertrand, Philippe
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3354
AB  - Dissymmetric cross metathesis of alkenes as a convergent and general synthetic strategy allowed for the preparation of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Bocprotected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability to stimulate the expression of the epithelial marker E-cadherin and tumor suppressor genes like SEMA3F and p21, suggesting a potential use of this compound for lung cancer treatment. Molecular docking on all 11 HDAC isoforms was used to rationalize the observed biological results.
PB  - Amer Chemical Soc, Washington
T2  - ACS Medicinal Chemistry Letters
T1  - Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling
VL  - 10
IS  - 6
SP  - 863
EP  - 868
DO  - 10.1021/acsmedchemlett.8b00440
ER  - 

@article{
author = "Bouchet, Samuel and Linot, Camille and Ružić, Dušan and Agbaba, Danica and Fouchaq, Benoit and Roche, Joelle and Nikolić, Katarina and Blanquart, Christophe and Bertrand, Philippe",
year = "2019",
abstract = "Dissymmetric cross metathesis of alkenes as a convergent and general synthetic strategy allowed for the preparation of a new small series of human histone deacetylases (HDAC) inhibitors. Alkenes bearing Bocprotected hydroxamic acid and benzamide and trityl-protected thiols were used to provide the zinc binding groups and were reacted with alkenes bearing aromatic cap groups. One compound was identified as a selective HDAC6 inhibitor lead. Additional biological evaluation in cancer cell lines demonstrated its ability to stimulate the expression of the epithelial marker E-cadherin and tumor suppressor genes like SEMA3F and p21, suggesting a potential use of this compound for lung cancer treatment. Molecular docking on all 11 HDAC isoforms was used to rationalize the observed biological results.",
publisher = "Amer Chemical Soc, Washington",
journal = "ACS Medicinal Chemistry Letters",
title = "Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling",
volume = "10",
number = "6",
pages = "863-868",
doi = "10.1021/acsmedchemlett.8b00440"
}

Bouchet, S., Linot, C., Ružić, D., Agbaba, D., Fouchaq, B., Roche, J., Nikolić, K., Blanquart, C.,& Bertrand, P.. (2019). Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling. in ACS Medicinal Chemistry Letters
Amer Chemical Soc, Washington., 10(6), 863-868.
https://doi.org/10.1021/acsmedchemlett.8b00440

Bouchet S, Linot C, Ružić D, Agbaba D, Fouchaq B, Roche J, Nikolić K, Blanquart C, Bertrand P. Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling. in ACS Medicinal Chemistry Letters. 2019;10(6):863-868.
doi:10.1021/acsmedchemlett.8b00440 .

Bouchet, Samuel, Linot, Camille, Ružić, Dušan, Agbaba, Danica, Fouchaq, Benoit, Roche, Joelle, Nikolić, Katarina, Blanquart, Christophe, Bertrand, Philippe, "Extending Cross Metathesis To Identify Selective HDAC Inhibitors: Synthesis, Biological Activities, and Modeling" in ACS Medicinal Chemistry Letters, 10, no. 6 (2019):863-868,
https://doi.org/10.1021/acsmedchemlett.8b00440 . .

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  - Čarapić, Marija
AU  - Nikolić, Katarina
AU  - Marković, Bojan
AU  - Petković, Miloš
AU  - Pavlović, Milena
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3329
AB  - The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.
PB  - Wiley, Hoboken
T2  - Biomedical Chromatography
T1  - Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities
VL  - 33
IS  - 2
DO  - 10.1002/bmc.4384
ER  - 

@article{
author = "Čarapić, Marija and Nikolić, Katarina and Marković, Bojan and Petković, Miloš and Pavlović, Milena and Agbaba, Danica",
year = "2019",
abstract = "The separation and characterization of the unknown degradation product of second-generation antipsychotic drug ziprasidone are essential for defining the genotoxic potential of the compound. The aim of this study was to develop a simple UHPLC method coupled with tandem mass spectrometry (MS/MS) for chemical characterization of an unknown degradant, and the separation and quantification of ziprasidone and its five main impurities (I-V) in the raw material and pharmaceuticals. Chromatographic conditions were optimized by experimental design. The MS/MS fragmentation conditions were optimized individually for each compound in order to obtain both specific fragments and high signal intensity. A rapid and sensitive UHPLC-MS/MS method was developed. All seven analytes were eluted within the 7 min run time. The best separation was obtained on the Acquity UPLC BEH C-18 (50 x 2.1 mm x 1.7 mu m) column in gradient mode with ammonium-formate buffer (10 mm; pH 4.7) and acetonitrile as mobile phase, with the flow rate of 0.3 mL min(-1) and at the column temperature of 30 degrees C. The new UHPLC-MS/MS method was fully validated and all validation parameters were confirmed. The fragmentation pathways and chemical characterization of an unknown degradant were proposed and it was confirmed that there are no structural alerts concerning genotoxicity.",
publisher = "Wiley, Hoboken",
journal = "Biomedical Chromatography",
title = "Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities",
volume = "33",
number = "2",
doi = "10.1002/bmc.4384"
}

Čarapić, M., Nikolić, K., Marković, B., Petković, M., Pavlović, M.,& Agbaba, D.. (2019). Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities. in Biomedical Chromatography
Wiley, Hoboken., 33(2).
https://doi.org/10.1002/bmc.4384

Čarapić M, Nikolić K, Marković B, Petković M, Pavlović M, Agbaba D. Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities. in Biomedical Chromatography. 2019;33(2).
doi:10.1002/bmc.4384 .

Čarapić, Marija, Nikolić, Katarina, Marković, Bojan, Petković, Miloš, Pavlović, Milena, Agbaba, Danica, "Ultra-performance liquid chromatography tandem mass spectrometry for the rapid, simultaneous analysis of ziprasidone and its impurities" in Biomedical Chromatography, 33, no. 2 (2019),
https://doi.org/10.1002/bmc.4384 . .

TY  - JOUR
AU  - Radulović, Valentina
AU  - Aleksić, Mara
AU  - Kapetanović, Vera
AU  - Rajić, K.K
AU  - Jovanović, M
AU  - Marjanović, I
AU  - Stojković, M
AU  - Agbaba, Danica
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3286
AB  - A novel voltammetric method was developed for brimonidine (BRIM) determination in deproteinized aqueous humor, simplifying preparation of biological samples for analysis for stability studies. The differential pulse voltammetric (DPV) method using boron doped diamond electrode (BDDE), based on characteristic oxidation peaks, was proposed and successfully applied. The linearity range was within 5.0 × 10−6 to 5.0 × 10−5 M of brimonidine, and limit of detection and limit of quantitation were 1.94 × 10−6 M and 6.46 × 10−6 M, respectively. Intra-day and inter-day precision and accuracy were evaluated and all results were in accordance with validation ICH guidelines. The best short-term stability study results were obtained for a concentration level of 3.0 × 10−5 M expressed by deviation of + 1.86% between initial and post storage concentrations. A long-term stability study was performed for two concentrations of 3.0 × 10−5 M and 5.0 × 10−5 M and resulted in deviations of + 1.63% and + 3.56%, respectively. A freeze and thaw stability study indicated that samples might be frozen only once. The enhancement of DPV/BDDE method sensitivity gained by modification, for the analysis of immeasurable BRIM quantities in native, untreated aqueous humor, was reached for quantities of 6 or 12 nmol/0.1 mL aqueous humor with acceptable accuracy (up to + 7.5%). The nature of the process—the irreversible one electron oxidation voltammetric peak of BRIM—limited the sensitivity. Only electrochemical pre-treatment of the BDD electrode before each measurement significantly speeded up the whole procedure. The advantages of the proposed method are simplicity, short-time performance, and good specificity/selectivity, as well as satisfactory accuracy, and no chemical modification of BDDE was necessary.
PB  - Springer Verlag
T2  - Analytical and Bioanalytical Chemistry
T1  - The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method—possible application for direct assay in native samples
DO  - 10.1007/s00216-019-01955-3
ER  - 

@article{
author = "Radulović, Valentina and Aleksić, Mara and Kapetanović, Vera and Rajić, K.K and Jovanović, M and Marjanović, I and Stojković, M and Agbaba, Danica",
year = "2019",
abstract = "A novel voltammetric method was developed for brimonidine (BRIM) determination in deproteinized aqueous humor, simplifying preparation of biological samples for analysis for stability studies. The differential pulse voltammetric (DPV) method using boron doped diamond electrode (BDDE), based on characteristic oxidation peaks, was proposed and successfully applied. The linearity range was within 5.0 × 10−6 to 5.0 × 10−5 M of brimonidine, and limit of detection and limit of quantitation were 1.94 × 10−6 M and 6.46 × 10−6 M, respectively. Intra-day and inter-day precision and accuracy were evaluated and all results were in accordance with validation ICH guidelines. The best short-term stability study results were obtained for a concentration level of 3.0 × 10−5 M expressed by deviation of + 1.86% between initial and post storage concentrations. A long-term stability study was performed for two concentrations of 3.0 × 10−5 M and 5.0 × 10−5 M and resulted in deviations of + 1.63% and + 3.56%, respectively. A freeze and thaw stability study indicated that samples might be frozen only once. The enhancement of DPV/BDDE method sensitivity gained by modification, for the analysis of immeasurable BRIM quantities in native, untreated aqueous humor, was reached for quantities of 6 or 12 nmol/0.1 mL aqueous humor with acceptable accuracy (up to + 7.5%). The nature of the process—the irreversible one electron oxidation voltammetric peak of BRIM—limited the sensitivity. Only electrochemical pre-treatment of the BDD electrode before each measurement significantly speeded up the whole procedure. The advantages of the proposed method are simplicity, short-time performance, and good specificity/selectivity, as well as satisfactory accuracy, and no chemical modification of BDDE was necessary.",
publisher = "Springer Verlag",
journal = "Analytical and Bioanalytical Chemistry",
title = "The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method—possible application for direct assay in native samples",
doi = "10.1007/s00216-019-01955-3"
}

Radulović, V., Aleksić, M., Kapetanović, V., Rajić, K.K, Jovanović, M., Marjanović, I., Stojković, M.,& Agbaba, D.. (2019). The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method—possible application for direct assay in native samples. in Analytical and Bioanalytical Chemistry
Springer Verlag..
https://doi.org/10.1007/s00216-019-01955-3

Radulović V, Aleksić M, Kapetanović V, Rajić K, Jovanović M, Marjanović I, Stojković M, Agbaba D. The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method—possible application for direct assay in native samples. in Analytical and Bioanalytical Chemistry. 2019;.
doi:10.1007/s00216-019-01955-3 .

Radulović, Valentina, Aleksić, Mara, Kapetanović, Vera, Rajić, K.K, Jovanović, M, Marjanović, I, Stojković, M, Agbaba, Danica, "The evaluation of short- and long-term stability studies for brimonidine in aqueous humor by DPV/BDDE method—possible application for direct assay in native samples" in Analytical and Bioanalytical Chemistry (2019),
https://doi.org/10.1007/s00216-019-01955-3 . .

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Jovanović, Milan
AU  - Nikolić, Katarina
AU  - Gagić, Žarko
AU  - Agbaba, Danica
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3099
AB  - The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs.
AB  - Značaj aktivacije fosfatidilinozitol-3-kinaza (PI3K) u procesima nastanka i rasta ćelija karcinoma doveo je do velikog interesovanja za razvijanje novih antitumorskih lekova koji inhibiraju PI3K-Akt signalni put. Najnovija istraživanja pokazuju da je kod većine tipova karcinoma izmenjena aktivnost p110α izoforme PI3K kinaze, te se danas poseban akcenat stavlja na razvijanje specifičnih PI3K-α inhibitora. Na seriji od 92 PI3K-α inhibitora, čiji su podaci o eksperimentalno određenoj inhibitornoj aktivnosti prikupljeni iz literature, sprovedene su 3D studije kvantitativnog odnosa između strukture i dejstva (3D-QSAR). Sve molekulske strukture su prethodno optimizovane upotrebom semiempirijske PM3 i ab initio Hartree-Fock/3-21G metode, a modelovanje je vršeno primenom PLS regresione analize najmanjih kvadrata. Izračunati parametri interne (R2=0,84; Q2=0,67) i eksterne (R2pred=0,681; r2m=0,594; Δr2m=0,00039) validacije ukazuju na pouzdanost i dobru moć predviđanja formiranog 3DQSAR modela. Analizom varijabli određena je struktura farmakofore koja podrazumeva: prisustvo donora i akceptora vodonične veze na rastojanju 18-18,4 Å ili 12-12,4 Å; hidrofobni region na rastojanju od 15,2-15,6 Å od donora vodonične veze kao i prisustvo sternog centra na optimalnom rastojanju od donora i akceptora vodonične veze. Ovi rezultati će imati značaj u odabiru vodećih jedinjenja na kojima će biti moguće vršiti ciljane strukturne modifikacije za dizajniranje novih selektivnih PI3K-α inhibitora kao potencijalnih antineoplastika.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents
T1  - Molekulsko modelovanje i analiza 3D-strukture farmakofore selektivnih PI3K-α inhibitora kao antitumorskih agenasa
VL  - 68
IS  - 4
SP  - 860
EP  - 873
DO  - 10.5937/ArhFarm1804860J
ER  - 

@article{
author = "Jovanović, Milan and Nikolić, Katarina and Gagić, Žarko and Agbaba, Danica",
year = "2018",
abstract = "The importance of the activation of phosphatidylinositol-3-kinase (PI3K) in the processes of tumor cell formation and growth has brought great interest in the development of new antitumor drugs that inhibit the PI3K-Akt signaling pathway. Recent studies have shown that in most tumors the activity of p110α isoform of PI3K kinase has been altered, and today special emphasis is placed on developing specific PI3K-α inhibitors. In a series of 92 PI3K-α inhibitors, whose data on experimentally determined inhibitory activity were collected from literature, 3D quantitative structure-activity relationship studies (3D-QSAR) were carried out. All molecular structures were previously optimized using semiempirical PM3 and ab initio Hartree-Fock / 3- 21G methods, and modeling was performed using PLS regression analysis. Calculated parameters of internal (R2=0.84; Q2=0.67) and external (R2pred=0.681; r2m=0.594; Δr2m=0.00039)validation indicate on good reliability and predictive power of created 3D-QSAR model. The analysis of the variables enabled pharmacophore structure determination, which implies: presence of hydrogen bond donor and hydrogen bond acceptor at a distance of 18-18.4Å or 12- 12.4Å, presence of hydrophobic domain and hydrogen bond donor at a distance of 15.2-15.6Å, and presence of steric hotspot at optimal distance from hydrogen bond donor and acceptor. These results will have the relevance in selecting the lead compounds for targeted structural modifications in order to design new selective PI3K-α inhibitors as potential antitumor drugs., Značaj aktivacije fosfatidilinozitol-3-kinaza (PI3K) u procesima nastanka i rasta ćelija karcinoma doveo je do velikog interesovanja za razvijanje novih antitumorskih lekova koji inhibiraju PI3K-Akt signalni put. Najnovija istraživanja pokazuju da je kod većine tipova karcinoma izmenjena aktivnost p110α izoforme PI3K kinaze, te se danas poseban akcenat stavlja na razvijanje specifičnih PI3K-α inhibitora. Na seriji od 92 PI3K-α inhibitora, čiji su podaci o eksperimentalno određenoj inhibitornoj aktivnosti prikupljeni iz literature, sprovedene su 3D studije kvantitativnog odnosa između strukture i dejstva (3D-QSAR). Sve molekulske strukture su prethodno optimizovane upotrebom semiempirijske PM3 i ab initio Hartree-Fock/3-21G metode, a modelovanje je vršeno primenom PLS regresione analize najmanjih kvadrata. Izračunati parametri interne (R2=0,84; Q2=0,67) i eksterne (R2pred=0,681; r2m=0,594; Δr2m=0,00039) validacije ukazuju na pouzdanost i dobru moć predviđanja formiranog 3DQSAR modela. Analizom varijabli određena je struktura farmakofore koja podrazumeva: prisustvo donora i akceptora vodonične veze na rastojanju 18-18,4 Å ili 12-12,4 Å; hidrofobni region na rastojanju od 15,2-15,6 Å od donora vodonične veze kao i prisustvo sternog centra na optimalnom rastojanju od donora i akceptora vodonične veze. Ovi rezultati će imati značaj u odabiru vodećih jedinjenja na kojima će biti moguće vršiti ciljane strukturne modifikacije za dizajniranje novih selektivnih PI3K-α inhibitora kao potencijalnih antineoplastika.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents, Molekulsko modelovanje i analiza 3D-strukture farmakofore selektivnih PI3K-α inhibitora kao antitumorskih agenasa",
volume = "68",
number = "4",
pages = "860-873",
doi = "10.5937/ArhFarm1804860J"
}

Jovanović, M., Nikolić, K., Gagić, Ž.,& Agbaba, D.. (2018). Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(4), 860-873.
https://doi.org/10.5937/ArhFarm1804860J

Jovanović M, Nikolić K, Gagić Ž, Agbaba D. Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents. in Arhiv za farmaciju. 2018;68(4):860-873.
doi:10.5937/ArhFarm1804860J .

Jovanović, Milan, Nikolić, Katarina, Gagić, Žarko, Agbaba, Danica, "Molecular modeling and analysis of the 3D pharmacophore structure of the selective PI3K-α inhibitors as antitumor agents" in Arhiv za farmaciju, 68, no. 4 (2018):860-873,
https://doi.org/10.5937/ArhFarm1804860J . .

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

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

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

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

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

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

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

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

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

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