TY  - JOUR
AU  - Tubić, Biljana
AU  - Marković, Bojan
AU  - Vladimirov, Sandra
AU  - Ristić, Slavica M.
AU  - Ivković, Branka
AU  - Savić, Miroslav
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3024
AB  - A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum
VL  - 29
IS  - 2
SP  - 235
EP  - 252
DO  - 10.1556/1326.2017.29.2.7
ER  - 

@article{
author = "Tubić, Biljana and Marković, Bojan and Vladimirov, Sandra and Ristić, Slavica M. and Ivković, Branka and Savić, Miroslav and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum",
volume = "29",
number = "2",
pages = "235-252",
doi = "10.1556/1326.2017.29.2.7"
}

Tubić, B., Marković, B., Vladimirov, S., Ristić, S. M., Ivković, B., Savić, M., Poljarević, J.,& Sabo, T.. (2017). Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 29(2), 235-252.
https://doi.org/10.1556/1326.2017.29.2.7

Tubić B, Marković B, Vladimirov S, Ristić SM, Ivković B, Savić M, Poljarević J, Sabo T. Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica. 2017;29(2):235-252.
doi:10.1556/1326.2017.29.2.7 .

Tubić, Biljana, Marković, Bojan, Vladimirov, Sandra, Ristić, Slavica M., Ivković, Branka, Savić, Miroslav, Poljarević, Jelena, Sabo, Tibor, "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum" in Acta Chromatographica, 29, no. 2 (2017):235-252,
https://doi.org/10.1556/1326.2017.29.2.7 . .

TY  - JOUR
AU  - Petrović, Aleksandra
AU  - Petricević, Sasa M.
AU  - Ristić, Slavica M.
AU  - Ibrić, Svetlana
AU  - Simić, Slobodanka
AU  - Đurić, Zorica
AU  - Popović, Radmila
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2002
AB  - Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin (R) 350, tablets Purdue Frederic, Canada (R-II). Results: Calculated release rate constants and the f2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T-max, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest C-max (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). Discussion and conclusion: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.
PB  - Informa Healthcare, London
T2  - Drug Development and Industrial Pharmacy
T1  - Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms
VL  - 39
IS  - 6
SP  - 889
EP  - 900
DO  - 10.3109/03639045.2012.713364
ER  - 

@article{
author = "Petrović, Aleksandra and Petricević, Sasa M. and Ristić, Slavica M. and Ibrić, Svetlana and Simić, Slobodanka and Đurić, Zorica and Popović, Radmila",
year = "2013",
abstract = "Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin (R) 350, tablets Purdue Frederic, Canada (R-II). Results: Calculated release rate constants and the f2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T-max, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest C-max (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). Discussion and conclusion: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.",
publisher = "Informa Healthcare, London",
journal = "Drug Development and Industrial Pharmacy",
title = "Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms",
volume = "39",
number = "6",
pages = "889-900",
doi = "10.3109/03639045.2012.713364"
}

Petrović, A., Petricević, S. M., Ristić, S. M., Ibrić, S., Simić, S., Đurić, Z.,& Popović, R.. (2013). Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms. in Drug Development and Industrial Pharmacy
Informa Healthcare, London., 39(6), 889-900.
https://doi.org/10.3109/03639045.2012.713364

Petrović A, Petricević SM, Ristić SM, Ibrić S, Simić S, Đurić Z, Popović R. Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms. in Drug Development and Industrial Pharmacy. 2013;39(6):889-900.
doi:10.3109/03639045.2012.713364 .

Petrović, Aleksandra, Petricević, Sasa M., Ristić, Slavica M., Ibrić, Svetlana, Simić, Slobodanka, Đurić, Zorica, Popović, Radmila, "Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms" in Drug Development and Industrial Pharmacy, 39, no. 6 (2013):889-900,
https://doi.org/10.3109/03639045.2012.713364 . .

TY  - JOUR
AU  - Homšek, Irena
AU  - Popadić, Dragica
AU  - Simić, Slobodanka
AU  - Ristić, Slavica M.
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1613
AB  - Controlled-release (CR) pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ) CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC) based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.
AB  - Farmaceutske formulacije sa kontrolisanim oslobađanjem imaju nekoliko prednosti u odnosu na konvencionalne dozirane oblike sa trenutnim oslobađanjem iste lekovite supstance. To se pre svega ogleda u redukovanoj učestalosti doziranja, smanjenoj pojavi i/ili intenzitetu neželjenih efekata, većoj farmakološkoj selektivnosti, redukovanoj fluktuaciji lekovite supstance u plazmi i boljoj podnošljivosti. Kada se posle završene registracije preparat nađe na tržištu, može se javiti potreba za manjim izmenama u formulaciji. U isto vreme on treba da ostane efikasan i bezbedan za pacijente, što može biti potvrđeno na osnovu koncentracije lekovite supstance u plazmi i farmakokinetičkih podataka. Poseban izazov predstavlja predviđanje resorpcije i farmakokinetičkih osobina lekovite supstance kod ljudi na osnovu određivanja in vitro brzine rastvaranja i farmakokinetičkih podataka dobijenih ispitivanjem na životinjskom modelu. Zbog toga je cilj ovog ispitivanja bio da se uspostavi korelacija farmakokinetičkih parametara između modela kunića i humanog modela za formulacije tableta sa kontrolisanim oslobađanjem karbamazepina (KBZ) kao i in vitro in vivo korelacija zasnovana na predviđenoj frakciji resorbovanog leka. I pored uočenih razlika u srednjim profilima plazma koncentracija, rezultati koji se odnose na predviđenu frakciju resorbovane lekovite supstance bili su gotovo identični. Na osnovu toga se može zaključiti da se kunić može koristiti kao reprezentativan in vivo model za predviđanje farmakokinetičkih karakteristika formulacije sa kontrolisanim oslobađanjem KBZ kod ljudi.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Veterinarski glasnik
T1  - Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model
T1  - Predviđanje resorpcije i farmakokinetičkog profila karbamazepina iz tableta sa kontrolisanim oslobađanjem kod ljudi korišćenjem modela kunića
VL  - 65
IS  - 1-2
SP  - 71
EP  - 81
DO  - 10.2298/VETGL1102071H
ER  - 

@article{
author = "Homšek, Irena and Popadić, Dragica and Simić, Slobodanka and Ristić, Slavica M. and Vučićević, Katarina and Miljković, Branislava",
year = "2011",
abstract = "Controlled-release (CR) pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ) CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC) based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans., Farmaceutske formulacije sa kontrolisanim oslobađanjem imaju nekoliko prednosti u odnosu na konvencionalne dozirane oblike sa trenutnim oslobađanjem iste lekovite supstance. To se pre svega ogleda u redukovanoj učestalosti doziranja, smanjenoj pojavi i/ili intenzitetu neželjenih efekata, većoj farmakološkoj selektivnosti, redukovanoj fluktuaciji lekovite supstance u plazmi i boljoj podnošljivosti. Kada se posle završene registracije preparat nađe na tržištu, može se javiti potreba za manjim izmenama u formulaciji. U isto vreme on treba da ostane efikasan i bezbedan za pacijente, što može biti potvrđeno na osnovu koncentracije lekovite supstance u plazmi i farmakokinetičkih podataka. Poseban izazov predstavlja predviđanje resorpcije i farmakokinetičkih osobina lekovite supstance kod ljudi na osnovu određivanja in vitro brzine rastvaranja i farmakokinetičkih podataka dobijenih ispitivanjem na životinjskom modelu. Zbog toga je cilj ovog ispitivanja bio da se uspostavi korelacija farmakokinetičkih parametara između modela kunića i humanog modela za formulacije tableta sa kontrolisanim oslobađanjem karbamazepina (KBZ) kao i in vitro in vivo korelacija zasnovana na predviđenoj frakciji resorbovanog leka. I pored uočenih razlika u srednjim profilima plazma koncentracija, rezultati koji se odnose na predviđenu frakciju resorbovane lekovite supstance bili su gotovo identični. Na osnovu toga se može zaključiti da se kunić može koristiti kao reprezentativan in vivo model za predviđanje farmakokinetičkih karakteristika formulacije sa kontrolisanim oslobađanjem KBZ kod ljudi.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Veterinarski glasnik",
title = "Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model, Predviđanje resorpcije i farmakokinetičkog profila karbamazepina iz tableta sa kontrolisanim oslobađanjem kod ljudi korišćenjem modela kunića",
volume = "65",
number = "1-2",
pages = "71-81",
doi = "10.2298/VETGL1102071H"
}

Homšek, I., Popadić, D., Simić, S., Ristić, S. M., Vučićević, K.,& Miljković, B.. (2011). Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model. in Veterinarski glasnik
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 65(1-2), 71-81.
https://doi.org/10.2298/VETGL1102071H

Homšek I, Popadić D, Simić S, Ristić SM, Vučićević K, Miljković B. Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model. in Veterinarski glasnik. 2011;65(1-2):71-81.
doi:10.2298/VETGL1102071H .

Homšek, Irena, Popadić, Dragica, Simić, Slobodanka, Ristić, Slavica M., Vučićević, Katarina, Miljković, Branislava, "Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model" in Veterinarski glasnik, 65, no. 1-2 (2011):71-81,
https://doi.org/10.2298/VETGL1102071H . .

TY  - CONF
AU  - Ćupić, Vitomir
AU  - Petricević, S.
AU  - Ristić, Slavica M.
AU  - Simić, Slobodanka
AU  - Petrović, S.
AU  - Vučićević, Katarina
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1271
PB  - Wiley-Blackwell Publishing, Inc, Malden
C3  - Journal of Veterinary Pharmacology and Therapeutics
T1  - Comparison between pharmacokinetic parameters of sustained-release aminophylline tablets in rabbits
VL  - 32
IS  - Suppl. 1
SP  - 243
EP  - 243
DO  - 10.1111/j.1365-2885.2009.01091.x
ER  - 

@conference{
author = "Ćupić, Vitomir and Petricević, S. and Ristić, Slavica M. and Simić, Slobodanka and Petrović, S. and Vučićević, Katarina",
year = "2009",
publisher = "Wiley-Blackwell Publishing, Inc, Malden",
journal = "Journal of Veterinary Pharmacology and Therapeutics",
title = "Comparison between pharmacokinetic parameters of sustained-release aminophylline tablets in rabbits",
volume = "32",
number = "Suppl. 1",
pages = "243-243",
doi = "10.1111/j.1365-2885.2009.01091.x"
}

Ćupić, V., Petricević, S., Ristić, S. M., Simić, S., Petrović, S.,& Vučićević, K.. (2009). Comparison between pharmacokinetic parameters of sustained-release aminophylline tablets in rabbits. in Journal of Veterinary Pharmacology and Therapeutics
Wiley-Blackwell Publishing, Inc, Malden., 32(Suppl. 1), 243-243.
https://doi.org/10.1111/j.1365-2885.2009.01091.x

Ćupić V, Petricević S, Ristić SM, Simić S, Petrović S, Vučićević K. Comparison between pharmacokinetic parameters of sustained-release aminophylline tablets in rabbits. in Journal of Veterinary Pharmacology and Therapeutics. 2009;32(Suppl. 1):243-243.
doi:10.1111/j.1365-2885.2009.01091.x .

Ćupić, Vitomir, Petricević, S., Ristić, Slavica M., Simić, Slobodanka, Petrović, S., Vučićević, Katarina, "Comparison between pharmacokinetic parameters of sustained-release aminophylline tablets in rabbits" in Journal of Veterinary Pharmacology and Therapeutics, 32, no. Suppl. 1 (2009):243-243,
https://doi.org/10.1111/j.1365-2885.2009.01091.x . .