TY  - JOUR
AU  - Demisli, Sotiria
AU  - Galani, Eleni
AU  - Goulielmaki, Maria
AU  - Kyrilis, Fotios
AU  - Ilić, Tanja
AU  - Hamdi, Farzad
AU  - Crevar, Milkica
AU  - Kastritis, Panagiotis
AU  - Pletsa, Vasiliki
AU  - Nallet, Frédéric
AU  - Savić, Snežana
AU  - Xenakis, Aristotelis
AU  - Papadimitriou, Vassiliki
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4384
AB  - Hypothesis: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems. Experiments: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin. Findings: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.
PB  - Academic Press Inc.
T2  - Journal of Colloid and Interface Science
T1  - Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study
VL  - 634
SP  - 300
EP  - 313
DO  - 10.1016/j.jcis.2022.12.036
ER  - 

@article{
author = "Demisli, Sotiria and Galani, Eleni and Goulielmaki, Maria and Kyrilis, Fotios and Ilić, Tanja and Hamdi, Farzad and Crevar, Milkica and Kastritis, Panagiotis and Pletsa, Vasiliki and Nallet, Frédéric and Savić, Snežana and Xenakis, Aristotelis and Papadimitriou, Vassiliki",
year = "2023",
abstract = "Hypothesis: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems. Experiments: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin. Findings: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.",
publisher = "Academic Press Inc.",
journal = "Journal of Colloid and Interface Science",
title = "Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study",
volume = "634",
pages = "300-313",
doi = "10.1016/j.jcis.2022.12.036"
}

Demisli, S., Galani, E., Goulielmaki, M., Kyrilis, F., Ilić, T., Hamdi, F., Crevar, M., Kastritis, P., Pletsa, V., Nallet, F., Savić, S., Xenakis, A.,& Papadimitriou, V.. (2023). Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study. in Journal of Colloid and Interface Science
Academic Press Inc.., 634, 300-313.
https://doi.org/10.1016/j.jcis.2022.12.036

Demisli S, Galani E, Goulielmaki M, Kyrilis F, Ilić T, Hamdi F, Crevar M, Kastritis P, Pletsa V, Nallet F, Savić S, Xenakis A, Papadimitriou V. Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study. in Journal of Colloid and Interface Science. 2023;634:300-313.
doi:10.1016/j.jcis.2022.12.036 .

Demisli, Sotiria, Galani, Eleni, Goulielmaki, Maria, Kyrilis, Fotios, Ilić, Tanja, Hamdi, Farzad, Crevar, Milkica, Kastritis, Panagiotis, Pletsa, Vasiliki, Nallet, Frédéric, Savić, Snežana, Xenakis, Aristotelis, Papadimitriou, Vassiliki, "Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study" in Journal of Colloid and Interface Science, 634 (2023):300-313,
https://doi.org/10.1016/j.jcis.2022.12.036 . .

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

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

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

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

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

TY  - JOUR
AU  - Savić, Jelena
AU  - Antonijević, Marija
AU  - Crevar, Milkica
AU  - Brborić, Jasmina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4978
AB  - Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination.
AB  - Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site
T1  - Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2
VL  - 73
IS  - 3
SP  - 205
EP  - 215
DO  - 10.5937/arhfarm73-44720
ER  - 

@article{
author = "Savić, Jelena and Antonijević, Marija and Crevar, Milkica and Brborić, Jasmina",
year = "2023",
abstract = "Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination., Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site, Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2",
volume = "73",
number = "3",
pages = "205-215",
doi = "10.5937/arhfarm73-44720"
}

Savić, J., Antonijević, M., Crevar, M.,& Brborić, J.. (2023). Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(3), 205-215.
https://doi.org/10.5937/arhfarm73-44720

Savić J, Antonijević M, Crevar M, Brborić J. Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju. 2023;73(3):205-215.
doi:10.5937/arhfarm73-44720 .

Savić, Jelena, Antonijević, Marija, Crevar, Milkica, Brborić, Jasmina, "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site" in Arhiv za farmaciju, 73, no. 3 (2023):205-215,
https://doi.org/10.5937/arhfarm73-44720 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Crevar, Milkica
AU  - Čudina, Olivera
AU  - Dobričić, Vladimir
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5453
AB  - The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1].
Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it.
According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was
chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of
organic modifier in the mobile phase).
Logk = logkw + aS (1)
ϕ0 = - logkw/a (2)
On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).
PB  - Aristotle University, Greece
PB  - Paul Ehrlich MedChem EuroPhD Network
C3  - MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts
T1  - Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis
SP  - 116
EP  - 116
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5453
ER  - 

@conference{
author = "Bošković, Jelena and Crevar, Milkica and Čudina, Olivera and Dobričić, Vladimir",
year = "2023",
abstract = "The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1].
Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it.
According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was
chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of
organic modifier in the mobile phase).
Logk = logkw + aS (1)
ϕ0 = - logkw/a (2)
On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).",
publisher = "Aristotle University, Greece, Paul Ehrlich MedChem EuroPhD Network",
journal = "MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts",
title = "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis",
pages = "116-116",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5453"
}

Bošković, J., Crevar, M., Čudina, O.,& Dobričić, V.. (2023). Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts
Aristotle University, Greece., 116-116.
https://hdl.handle.net/21.15107/rcub_farfar_5453

Bošković J, Crevar M, Čudina O, Dobričić V. Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts. 2023;:116-116.
https://hdl.handle.net/21.15107/rcub_farfar_5453 .

Bošković, Jelena, Crevar, Milkica, Čudina, Olivera, Dobričić, Vladimir, "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis" in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts (2023):116-116,
https://hdl.handle.net/21.15107/rcub_farfar_5453 .

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Đuriš, Jelena
AU  - Cvijić, Sandra
AU  - Crevar, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović-Stanojević, Nevena
AU  - Karanović, Danijela
AU  - Ivanov, Milan
AU  - Jovović, Đurđica
AU  - Vajić, Una-Jovana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4932
AB  - In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.
PB  - Elsevier
T2  - Journal of Drug Delivery Science and Technology
T1  - Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films
VL  - 86
DO  - 10.1016/j.jddst.2023.104715
ER  - 

@article{
author = "Kurćubić, Ivana and Đuriš, Jelena and Cvijić, Sandra and Crevar, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović-Stanojević, Nevena and Karanović, Danijela and Ivanov, Milan and Jovović, Đurđica and Vajić, Una-Jovana",
year = "2023",
abstract = "In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.",
publisher = "Elsevier",
journal = "Journal of Drug Delivery Science and Technology",
title = "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films",
volume = "86",
doi = "10.1016/j.jddst.2023.104715"
}

Kurćubić, I., Đuriš, J., Cvijić, S., Crevar, M., Ibrić, S., Miloradović, Z., Mihailović-Stanojević, N., Karanović, D., Ivanov, M., Jovović, Đ.,& Vajić, U.. (2023). Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology
Elsevier., 86.
https://doi.org/10.1016/j.jddst.2023.104715

Kurćubić I, Đuriš J, Cvijić S, Crevar M, Ibrić S, Miloradović Z, Mihailović-Stanojević N, Karanović D, Ivanov M, Jovović Đ, Vajić U. Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology. 2023;86.
doi:10.1016/j.jddst.2023.104715 .

Kurćubić, Ivana, Đuriš, Jelena, Cvijić, Sandra, Crevar, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović-Stanojević, Nevena, Karanović, Danijela, Ivanov, Milan, Jovović, Đurđica, Vajić, Una-Jovana, "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films" in Journal of Drug Delivery Science and Technology, 86 (2023),
https://doi.org/10.1016/j.jddst.2023.104715 . .

TY  - JOUR
AU  - Ivković, Branka
AU  - Crevar, Milkica
AU  - Cvetanović, Anka
AU  - Ubavkić, Katarina
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4435
AB  - Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream
VL  - 35
IS  - 1
SP  - 46
EP  - 51
DO  - 10.1556/1326.2021.00998
ER  - 

@article{
author = "Ivković, Branka and Crevar, Milkica and Cvetanović, Anka and Ubavkić, Katarina and Marković, Bojan",
year = "2023",
abstract = "Corticosteroids are anti-inflammatory and immunosuppressant drugs. Topical corticosteroids formulations (ointments, creams, gels) are used in the treatment of different types of dermatitis and urticaria. Considering their therapeutic and whitening effects, they are frequently used for counterfeiting of cosmetic products. Corticosteroids can cause different local and systemic side effects. HPLC method is often chosen for their analysis, because it is selective, sensitive, precise, simple and fast. The aim of this study was optimization and validation of RP-HPLC method with UV detection for determination of trace levels of corticosteroids in ambiphilic creams. This method is used for qualitative and quantitative analysis of evaluated corticosteroids. Mometasone furoate, hydrocortisone acetate, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone dipropionate and triamcinolone acetonide were evaluated. Separation was performed on Inertsil® ODS-3V 250 × 4.6 mm, 5 μm chromatographic column. Mobile phase was mixture of acetonitrile and water 50:50 (v/v) with gradient elution and flow rate 1 mL min-1. Column temperature was held on 40 °C and UV detection was performed at 240 nm. Selectivity, linearity, accuracy, precision and limit of quantification (LOQ) were evaluated. Method is selective because ambiphilic cream base peaks and corticosteroids peaks were not overlapping. Linearity was confirmed since correlation coefficient was 1 for all compounds. Accuracy and precision were evaluated for hydrocortisone acetate and betamethasone dipropionate. Determined Recovery values were in range of 70-130%. Both RSD values (21.46% and 9.59%) were lower than 30%. Method is highly sensitive since LOQ concentrations were in ng mL-1 range. All evaluated parameters of validation were in accordance with regulatory requirements. Validated RP-HPLC method can be used for qualitative and quantitative analysis of selected corticosteroids in ambiphilic creams.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream",
volume = "35",
number = "1",
pages = "46-51",
doi = "10.1556/1326.2021.00998"
}

Ivković, B., Crevar, M., Cvetanović, A., Ubavkić, K.,& Marković, B.. (2023). Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 46-51.
https://doi.org/10.1556/1326.2021.00998

Ivković B, Crevar M, Cvetanović A, Ubavkić K, Marković B. Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream. in Acta Chromatographica. 2023;35(1):46-51.
doi:10.1556/1326.2021.00998 .

Ivković, Branka, Crevar, Milkica, Cvetanović, Anka, Ubavkić, Katarina, Marković, Bojan, "Development and validation of RP-HPLC method for quantification of trace levels of topical corticosteroids in ambiphilic cream" in Acta Chromatographica, 35, no. 1 (2023):46-51,
https://doi.org/10.1556/1326.2021.00998 . .

TY  - CONF
AU  - Crevar, Milkica
AU  - Guzonjić, Azra
AU  - Kotur-Stevuljević, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4444
AB  - Oxidative stress is a phenomenon that occurs due to the disturbance in the balance
between the production of reactive oxygen species and the ability of biological systems to
remove the resulting compounds. Oxidative stress is involved in the pathogenesis of many
disorders in the human organism. This indicates the importance of quantification of
oxidative stress parameters in biological samples. Traditionally, these parameters are
determined by biochemical tests. Although these tests are routinely performed, they have
many drawbacks. To determine the exact concentration of selected compounds, more
sensitive analytical methods are becoming more important. In the modern scientific
literature, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly
mentioned (1). This method, with adequate selection of stationary and mobile phases,
enables quantification of very low concentrations of selected parameters. In addition, these
methods can simultaneously determine the concentration of many selected components.
However, it is necessary to take into account that LC-MS/MS methods require a very purified
biological sample from which the proteins have been maximally removed. In this work, we
will present the results of determination of cysteine, cystine, reduced and oxidized
glutathione in patients with microcellular lung cancer. The use of LC-MS/MS methods is
becoming increasingly common for the analysis of oxidative stress markers in biological
fluids. In the future, we are expected to move to even more modern, fully automated
methods, which simultaneously purify and analyze samples.
AB  - Oksidativni stres je pojava koja nastaje usled narušavanja ravnoteže između
proizvodnje i nagomilavanja reaktivnih jedinjenja kiseonika u organizmu i sposobnosti
bioloških sistema da ukloni nastala jedinjenja. Oksidativni stres učestvuje u patogenezi
mnogih poremećaja kao što su kardiovaskularne bolesti, dijabetes i bolesti bubrega. Ovo
ukazuje na značaj određivanja odabranih parametara oksidativnog stresa u uzorcima
biološkog materijala. Tradicionalno, najveći broj parametara se određuje biohemijskim
testovima. Iako se ovi testovi rutinski izvode, oni imaju mnoge nedostatke. Da bi se odredila
tačna koncentracija izabranih parametara, koji se u uzorcima nalaze u veoma niskim
koncentracijama, sve veću prednost imaju osetljivije analitičke metode. U savremenoj
naučnoj literaturi se u te svrhe sve više spominje tečna hromatografija spregnuta sa
masenim detektorom (LC-MS/MS) (1). Ova metoda, uz adekvatan izbor stacionarne i
mobilne faze, omogućava kvantifikaciju veoma niskih koncentracija odabranih jedinjenja.
Sem toga, ovim metodama se istovremeno, u jednom uzorku, može odrediti koncentracija
većeg broja odabranih komponenti. Ipak, neophodno je voditi računa o tome da tečna
hromatografija spregnuta sa masenim detektorom zahteva dobro prečišćen uzorak biološkog
materijala iz kog su maksimalno uklonjeni proteini. U ovom radu biće prikazani rezultati
određivanja cisteina, cistina, redukovanog i oksidovanog glutationa kod pacijenata sa
mikrocelularnim karcinomom pluća. Upotreba LC-MS/MS metoda je sve uobičajenija za
analizu markera oksidativnog stresa u biološkim tečnostima zbog svoje osetljivosti. U
budućnosti se očekuje razvoj ka još savremenijim, potpuno automatizovanim metodama,
kojima se istovremeno uzorci prečišćavaju i analiziraju.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of LC-MS/MS methods in the quantification of oxidative stress parameters
T1  - Primena LC‐MS/MS metoda u ispitivanju parametara oksidativnog stresa
VL  - 72
IS  - 4 suplement
SP  - S51
EP  - S52
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4444
ER  - 

@conference{
author = "Crevar, Milkica and Guzonjić, Azra and Kotur-Stevuljević, Jelena",
year = "2022",
abstract = "Oxidative stress is a phenomenon that occurs due to the disturbance in the balance
between the production of reactive oxygen species and the ability of biological systems to
remove the resulting compounds. Oxidative stress is involved in the pathogenesis of many
disorders in the human organism. This indicates the importance of quantification of
oxidative stress parameters in biological samples. Traditionally, these parameters are
determined by biochemical tests. Although these tests are routinely performed, they have
many drawbacks. To determine the exact concentration of selected compounds, more
sensitive analytical methods are becoming more important. In the modern scientific
literature, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly
mentioned (1). This method, with adequate selection of stationary and mobile phases,
enables quantification of very low concentrations of selected parameters. In addition, these
methods can simultaneously determine the concentration of many selected components.
However, it is necessary to take into account that LC-MS/MS methods require a very purified
biological sample from which the proteins have been maximally removed. In this work, we
will present the results of determination of cysteine, cystine, reduced and oxidized
glutathione in patients with microcellular lung cancer. The use of LC-MS/MS methods is
becoming increasingly common for the analysis of oxidative stress markers in biological
fluids. In the future, we are expected to move to even more modern, fully automated
methods, which simultaneously purify and analyze samples., Oksidativni stres je pojava koja nastaje usled narušavanja ravnoteže između
proizvodnje i nagomilavanja reaktivnih jedinjenja kiseonika u organizmu i sposobnosti
bioloških sistema da ukloni nastala jedinjenja. Oksidativni stres učestvuje u patogenezi
mnogih poremećaja kao što su kardiovaskularne bolesti, dijabetes i bolesti bubrega. Ovo
ukazuje na značaj određivanja odabranih parametara oksidativnog stresa u uzorcima
biološkog materijala. Tradicionalno, najveći broj parametara se određuje biohemijskim
testovima. Iako se ovi testovi rutinski izvode, oni imaju mnoge nedostatke. Da bi se odredila
tačna koncentracija izabranih parametara, koji se u uzorcima nalaze u veoma niskim
koncentracijama, sve veću prednost imaju osetljivije analitičke metode. U savremenoj
naučnoj literaturi se u te svrhe sve više spominje tečna hromatografija spregnuta sa
masenim detektorom (LC-MS/MS) (1). Ova metoda, uz adekvatan izbor stacionarne i
mobilne faze, omogućava kvantifikaciju veoma niskih koncentracija odabranih jedinjenja.
Sem toga, ovim metodama se istovremeno, u jednom uzorku, može odrediti koncentracija
većeg broja odabranih komponenti. Ipak, neophodno je voditi računa o tome da tečna
hromatografija spregnuta sa masenim detektorom zahteva dobro prečišćen uzorak biološkog
materijala iz kog su maksimalno uklonjeni proteini. U ovom radu biće prikazani rezultati
određivanja cisteina, cistina, redukovanog i oksidovanog glutationa kod pacijenata sa
mikrocelularnim karcinomom pluća. Upotreba LC-MS/MS metoda je sve uobičajenija za
analizu markera oksidativnog stresa u biološkim tečnostima zbog svoje osetljivosti. U
budućnosti se očekuje razvoj ka još savremenijim, potpuno automatizovanim metodama,
kojima se istovremeno uzorci prečišćavaju i analiziraju.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of LC-MS/MS methods in the quantification of oxidative stress parameters, Primena LC‐MS/MS metoda u ispitivanju parametara oksidativnog stresa",
volume = "72",
number = "4 suplement",
pages = "S51-S52",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4444"
}

Crevar, M., Guzonjić, A.,& Kotur-Stevuljević, J.. (2022). Application of LC-MS/MS methods in the quantification of oxidative stress parameters. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S51-S52.
https://hdl.handle.net/21.15107/rcub_farfar_4444

Crevar M, Guzonjić A, Kotur-Stevuljević J. Application of LC-MS/MS methods in the quantification of oxidative stress parameters. in Arhiv za farmaciju. 2022;72(4 suplement):S51-S52.
https://hdl.handle.net/21.15107/rcub_farfar_4444 .

Crevar, Milkica, Guzonjić, Azra, Kotur-Stevuljević, Jelena, "Application of LC-MS/MS methods in the quantification of oxidative stress parameters" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S51-S52,
https://hdl.handle.net/21.15107/rcub_farfar_4444 .

TY  - CONF
AU  - Miličević, Maja
AU  - Crevar, Milkica
AU  - Ivković, Branka
AU  - Džudović, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4599
AB  - Rivaroxaban belongs to the group of direct oral anticoagulants (DOAC), drugs used to
prevent and treat venous thrombosis and venous thromboembolism. Drugs from this group
are considered safer than vitamin K antagonists. In case of overdose, their most significant
side effect is bleeding. Given the great toxicological significance, it is very important to
develop an analytical method for quantification of this drug in biological samples. The liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of
rivaroxaban content in plasma samples was optimized and validated. Plasma samples were
prepared by protein precipitation with cold acetonitrile. Carbamazepine was used as an
internal standard. The analysis was performed on an Infinity Lab Poroshell 120 EC-C18, 4.6
×100 mm, 2.7 μm chromatographic column. The mobile phase consisted of acetonitrile and
0.1% formic acid (50:50, v/v), at a flow rate of 400 μL/min and a column temperature set at
30°C. The autosampler temperature was 4C. The injection volume was 10 μL. Detection of
analytes and internal standard was performed in multireaction monitoring mode (MRM), at
the following ion transitions: 437>145 (m/z) for rivaroxaban, and 237>194 (m/z) for the
internal standard. The optimized method was validated and the obtained parameters
indicate that the method is sensitive, specific, selective, precise and accurate. The samples
were stable under the tested conditions. A validated method has been used to determine the
concentration of rivaroxaban in plasma samples of patients with atrial fibrillation who were
hospitalized under strict medical supervision. Obtained concentrations were in the expected
range.
AB  - Rivaroksaban pripada grupi direktnih oralnih antikoagulanasa (DOAK), lekova koji se
koriste za prevenciju i lečenje venske tromboze i venske tromboembolije. Lekovi iz ove
grupe se smatraju bezbednijim od antagonista vitamina K. U slučaju predoziranja, njihov
najznačajniji neželjeni efekat je krvarenje. S obzirom na veliki toksikološki značaj, veoma je
važno postojanje analitičke metode za određivanje sadržaja ovog leka u uzorcima biološkog
materijala. Optimizovana je i validirana metoda tečne hromatografije spregnute sa masenom
spektrometrijom (LC-MS/MS) za određivanje sadržaja rivaroksabana u uzorcima plazme.
Uzorci plazme su pripremani metodom precipitacije proteina koja je vršena hladnim
acetonitrilom. Kao interni standard korišćen je karbamazepin. Analiza je izvršena na Infinity
Lab Poroshell 120 EC-C18, 4,6×100 mm, 2,7 μm hromatografskoj koloni. Mobilna faza se
sastojala od acetonitrila i 0,1% mravlje kiseline (50:50, v/v), pri protoku od 400 μL/min i
temperaturi kolone podešenoj na 30°C. Temperatura autosemplera je bila 4C. Injekciona
zapremina je bila 10 μL. Detekcija analita i internog standarda je izvršena u multireakcionom
monitoring modu (MRM), pri sledećim jonskim prelazima: 437>145 (m/z) za rivaroksaban,
odnosno 237>194 (m/z) za interni standard. Optimizovana metoda je validirana i dobijeni
parametri ukazuju da je metoda osetljiva, specifična, selektivna, precizna i tačna. Uzorci su
stabilni pri ispitivanim uslovima. Validirana metoda je primenjena za određivanje
koncentracije rivaroksabana u uzorcima plazme pacijenata sa atrijalnom fibrilacijom, koji su
bili hospitalizovani, pod strogim medicinskim nadzorom. Određene koncentracije su bile u
očekivanom opsegu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples
T1  - Razvoj i validacija metode tečne hromatografije spregnute sa masenom spektrometrijom za određivanje sadržaja rivaroksabana u uzorcima plazme
VL  - 72
IS  - 4 suplement
SP  - S534
EP  - S535
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4599
ER  - 

@conference{
author = "Miličević, Maja and Crevar, Milkica and Ivković, Branka and Džudović, Jelena",
year = "2022",
abstract = "Rivaroxaban belongs to the group of direct oral anticoagulants (DOAC), drugs used to
prevent and treat venous thrombosis and venous thromboembolism. Drugs from this group
are considered safer than vitamin K antagonists. In case of overdose, their most significant
side effect is bleeding. Given the great toxicological significance, it is very important to
develop an analytical method for quantification of this drug in biological samples. The liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of
rivaroxaban content in plasma samples was optimized and validated. Plasma samples were
prepared by protein precipitation with cold acetonitrile. Carbamazepine was used as an
internal standard. The analysis was performed on an Infinity Lab Poroshell 120 EC-C18, 4.6
×100 mm, 2.7 μm chromatographic column. The mobile phase consisted of acetonitrile and
0.1% formic acid (50:50, v/v), at a flow rate of 400 μL/min and a column temperature set at
30°C. The autosampler temperature was 4C. The injection volume was 10 μL. Detection of
analytes and internal standard was performed in multireaction monitoring mode (MRM), at
the following ion transitions: 437>145 (m/z) for rivaroxaban, and 237>194 (m/z) for the
internal standard. The optimized method was validated and the obtained parameters
indicate that the method is sensitive, specific, selective, precise and accurate. The samples
were stable under the tested conditions. A validated method has been used to determine the
concentration of rivaroxaban in plasma samples of patients with atrial fibrillation who were
hospitalized under strict medical supervision. Obtained concentrations were in the expected
range., Rivaroksaban pripada grupi direktnih oralnih antikoagulanasa (DOAK), lekova koji se
koriste za prevenciju i lečenje venske tromboze i venske tromboembolije. Lekovi iz ove
grupe se smatraju bezbednijim od antagonista vitamina K. U slučaju predoziranja, njihov
najznačajniji neželjeni efekat je krvarenje. S obzirom na veliki toksikološki značaj, veoma je
važno postojanje analitičke metode za određivanje sadržaja ovog leka u uzorcima biološkog
materijala. Optimizovana je i validirana metoda tečne hromatografije spregnute sa masenom
spektrometrijom (LC-MS/MS) za određivanje sadržaja rivaroksabana u uzorcima plazme.
Uzorci plazme su pripremani metodom precipitacije proteina koja je vršena hladnim
acetonitrilom. Kao interni standard korišćen je karbamazepin. Analiza je izvršena na Infinity
Lab Poroshell 120 EC-C18, 4,6×100 mm, 2,7 μm hromatografskoj koloni. Mobilna faza se
sastojala od acetonitrila i 0,1% mravlje kiseline (50:50, v/v), pri protoku od 400 μL/min i
temperaturi kolone podešenoj na 30°C. Temperatura autosemplera je bila 4C. Injekciona
zapremina je bila 10 μL. Detekcija analita i internog standarda je izvršena u multireakcionom
monitoring modu (MRM), pri sledećim jonskim prelazima: 437>145 (m/z) za rivaroksaban,
odnosno 237>194 (m/z) za interni standard. Optimizovana metoda je validirana i dobijeni
parametri ukazuju da je metoda osetljiva, specifična, selektivna, precizna i tačna. Uzorci su
stabilni pri ispitivanim uslovima. Validirana metoda je primenjena za određivanje
koncentracije rivaroksabana u uzorcima plazme pacijenata sa atrijalnom fibrilacijom, koji su
bili hospitalizovani, pod strogim medicinskim nadzorom. Određene koncentracije su bile u
očekivanom opsegu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples, Razvoj i validacija metode tečne hromatografije spregnute sa masenom spektrometrijom za određivanje sadržaja rivaroksabana u uzorcima plazme",
volume = "72",
number = "4 suplement",
pages = "S534-S535",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4599"
}

Miličević, M., Crevar, M., Ivković, B.,& Džudović, J.. (2022). Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S534-S535.
https://hdl.handle.net/21.15107/rcub_farfar_4599

Miličević M, Crevar M, Ivković B, Džudović J. Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples. in Arhiv za farmaciju. 2022;72(4 suplement):S534-S535.
https://hdl.handle.net/21.15107/rcub_farfar_4599 .

Miličević, Maja, Crevar, Milkica, Ivković, Branka, Džudović, Jelena, "Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S534-S535,
https://hdl.handle.net/21.15107/rcub_farfar_4599 .