TY  - JOUR
AU  - Rakić, Anita
AU  - Miljković, Branislava
AU  - Pokrajac, Milena
AU  - Vučićević, Katarina
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/948
AB  - A selective, sensitive, and simple high-performance liquid chromatographic (HPLC) method was developed for the determination of moclobemide and its two major metabolites, Ro 12-5637 and Ro 12-8095, in human plasma. Sample preparation (0.5 ml of plasma) involved solid-phase extraction (SPE) using Speedisk (R) H2O-Philic DVB columns. Separations were performed on a Waters XTerra (TM) RP18 column (5 mu m, 150 mm x 4.6 mm). The mobile phase consisted of 10 mM KH2PO4 with 1% triethylamine (pH 3.9) and acetonitrile (93:17, v/v), and a flow-rate was 1.2 ml/min. The total run time was 13 min. UV detection was performed at 240 nm. Mean absolute recoveries were >= 90% and the limit of quantification (LOQ) for all analytes was 0.02 mg/l. Calibration curves were linear (r > 0.995) over a wide range of the analyte concentrations in plasma; thus, the method is suitable for different clinical studies when large variations in the drug/metabolites concentrations are observed. During a 5-day assay validation procedure the accuracy and precision were tested and proven (relative errors (RE)  lt = 13%; intra-day coefficient of variation (CV)  lt = 7%; inter-day CV  lt = 13%). Many drugs frequently used in the target patient population were evaluated for potential interference in order method selectivity to be ensured. The assay has been used in a clinical pharmacokinetic study to assess steady-state pharmacokinetics of moclobenide and two metabolites in depressive patients on mono- and combined therapy.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - High-performance liquid chromatographic method for the determination of moclobemide and its two major metabolites in human plasma
VL  - 43
IS  - 4
SP  - 1416
EP  - 1422
DO  - 10.1016/j.jpba.2006.10.032
ER  - 

@article{
author = "Rakić, Anita and Miljković, Branislava and Pokrajac, Milena and Vučićević, Katarina",
year = "2007",
abstract = "A selective, sensitive, and simple high-performance liquid chromatographic (HPLC) method was developed for the determination of moclobemide and its two major metabolites, Ro 12-5637 and Ro 12-8095, in human plasma. Sample preparation (0.5 ml of plasma) involved solid-phase extraction (SPE) using Speedisk (R) H2O-Philic DVB columns. Separations were performed on a Waters XTerra (TM) RP18 column (5 mu m, 150 mm x 4.6 mm). The mobile phase consisted of 10 mM KH2PO4 with 1% triethylamine (pH 3.9) and acetonitrile (93:17, v/v), and a flow-rate was 1.2 ml/min. The total run time was 13 min. UV detection was performed at 240 nm. Mean absolute recoveries were >= 90% and the limit of quantification (LOQ) for all analytes was 0.02 mg/l. Calibration curves were linear (r > 0.995) over a wide range of the analyte concentrations in plasma; thus, the method is suitable for different clinical studies when large variations in the drug/metabolites concentrations are observed. During a 5-day assay validation procedure the accuracy and precision were tested and proven (relative errors (RE)  lt = 13%; intra-day coefficient of variation (CV)  lt = 7%; inter-day CV  lt = 13%). Many drugs frequently used in the target patient population were evaluated for potential interference in order method selectivity to be ensured. The assay has been used in a clinical pharmacokinetic study to assess steady-state pharmacokinetics of moclobenide and two metabolites in depressive patients on mono- and combined therapy.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "High-performance liquid chromatographic method for the determination of moclobemide and its two major metabolites in human plasma",
volume = "43",
number = "4",
pages = "1416-1422",
doi = "10.1016/j.jpba.2006.10.032"
}

Rakić, A., Miljković, B., Pokrajac, M.,& Vučićević, K.. (2007). High-performance liquid chromatographic method for the determination of moclobemide and its two major metabolites in human plasma. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 43(4), 1416-1422.
https://doi.org/10.1016/j.jpba.2006.10.032

Rakić A, Miljković B, Pokrajac M, Vučićević K. High-performance liquid chromatographic method for the determination of moclobemide and its two major metabolites in human plasma. in Journal of Pharmaceutical and Biomedical Analysis. 2007;43(4):1416-1422.
doi:10.1016/j.jpba.2006.10.032 .

Rakić, Anita, Miljković, Branislava, Pokrajac, Milena, Vučićević, Katarina, "High-performance liquid chromatographic method for the determination of moclobemide and its two major metabolites in human plasma" in Journal of Pharmaceutical and Biomedical Analysis, 43, no. 4 (2007):1416-1422,
https://doi.org/10.1016/j.jpba.2006.10.032 . .

TY  - JOUR
AU  - Rakić, Anita
AU  - Miljković, Branislava
AU  - Pokrajac, Milena
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/527
AB  - The aim of this review is to explain genetic basis of interindividual variability in cytochrome P450 (CYP450) dependent drug metabolism and highlight the clinical significance of different polymorphisms. Nearly all CYP450 isoenzymes involved in drug metabolism have been shown to be polymorphic, although some of them are functionally well conserved (CYP2E1 and CYP3A4) in comparison with others (CYP2D6, CYP2C19 and CYP2C9). Genetic variability in drug metabolizing enzymes can be assessed at the level of phenotype (by investigating enzyme level/activity) and/or genotype (by determining which alleles are present). Polymorphism divides a population into at least two phenotypes: individuals with deficient metabolism are termed „poor metabolizers” (PM), as compared to normal or „extensive metabolizers” (EM). In case of CYP2D6, „ultrarapide metabolizers” (UM) with extremely high enzyme activity, have also been identified. The clinical significance of particular polymorphism depends on the importance of metabolic pathway under polymorphic control, therapeutic index (TI) of a drug and its active metabolites, and incidence of the polymorphism in a particular population. Therapeutic consequences vary from increased risk of adverse reactions in PM, to therapeutic failure at standard drug doses in UM (if drug metabolites are inactive). Drug dosage, especially for narrow TI drugs, should be adjusted to the metabolic capacity of a patient , by phenotyping/genotyping prior to drug therapy.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Genetic polymorphism of Cytochrome P450 isoenzymes
T1  - Genetički polimorfizam izoenzima Citohroma P450
VL  - 54
IS  - 1-2
SP  - 61
EP  - 76
UR  - https://hdl.handle.net/21.15107/rcub_farfar_527
ER  - 

@article{
author = "Rakić, Anita and Miljković, Branislava and Pokrajac, Milena",
year = "2004",
abstract = "The aim of this review is to explain genetic basis of interindividual variability in cytochrome P450 (CYP450) dependent drug metabolism and highlight the clinical significance of different polymorphisms. Nearly all CYP450 isoenzymes involved in drug metabolism have been shown to be polymorphic, although some of them are functionally well conserved (CYP2E1 and CYP3A4) in comparison with others (CYP2D6, CYP2C19 and CYP2C9). Genetic variability in drug metabolizing enzymes can be assessed at the level of phenotype (by investigating enzyme level/activity) and/or genotype (by determining which alleles are present). Polymorphism divides a population into at least two phenotypes: individuals with deficient metabolism are termed „poor metabolizers” (PM), as compared to normal or „extensive metabolizers” (EM). In case of CYP2D6, „ultrarapide metabolizers” (UM) with extremely high enzyme activity, have also been identified. The clinical significance of particular polymorphism depends on the importance of metabolic pathway under polymorphic control, therapeutic index (TI) of a drug and its active metabolites, and incidence of the polymorphism in a particular population. Therapeutic consequences vary from increased risk of adverse reactions in PM, to therapeutic failure at standard drug doses in UM (if drug metabolites are inactive). Drug dosage, especially for narrow TI drugs, should be adjusted to the metabolic capacity of a patient , by phenotyping/genotyping prior to drug therapy.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Genetic polymorphism of Cytochrome P450 isoenzymes, Genetički polimorfizam izoenzima Citohroma P450",
volume = "54",
number = "1-2",
pages = "61-76",
url = "https://hdl.handle.net/21.15107/rcub_farfar_527"
}

Rakić, A., Miljković, B.,& Pokrajac, M.. (2004). Genetic polymorphism of Cytochrome P450 isoenzymes. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 54(1-2), 61-76.
https://hdl.handle.net/21.15107/rcub_farfar_527

Rakić A, Miljković B, Pokrajac M. Genetic polymorphism of Cytochrome P450 isoenzymes. in Arhiv za farmaciju. 2004;54(1-2):61-76.
https://hdl.handle.net/21.15107/rcub_farfar_527 .

Rakić, Anita, Miljković, Branislava, Pokrajac, Milena, "Genetic polymorphism of Cytochrome P450 isoenzymes" in Arhiv za farmaciju, 54, no. 1-2 (2004):61-76,
https://hdl.handle.net/21.15107/rcub_farfar_527 .