혈장, 뇨 및 조직 중 JAK 억제제인 tofacitinib의 HPLC분석법 및 약물동력학 연구에의 적용

Alternative Title
Simple determination of tofacitinib, a JAK inhibitor, in plasma, urine and tissue homogenates by HPLC and its application to a pharmacokinetic study
Author(s)
김지은
Alternative Author(s)
Kim jieun
Advisor
김소희, 김수동
Department
글로벌제약임상대학원 글로벌제약임상약학과
Publisher
The Graduate School, Ajou University
Publication Year
2018-02
Language
eng
Keyword
HPLCtofacitinibLLOQprecisionaccuracypharmacokinetics
Alternative Abstract
Tofacitinib, a janus kinase inhibitor, was developed to treat rheumatoid arthritis. To evaluate its pharmacokinetic characteristics, a simple high-performance liquid chromatography method was developed to determine the tofacitinib levels in rat plasma, urine, and tissue homogenates using hydrocortisone as an internal standard. The mobile phase was an isocratic system of 10 mM ammonium acetate : acetonitrile = 69.5:30.5 at a flow rate of 1.0 mL/min. Chromatograms were monitored by an ultraviolet detector at 287 nm. The retention times for tofacitinib and hydrocortisone were 6.93 and 11.0 min, respectively, and the lower limits of quantification for tofacitinib in rat plasma and urine were 0.01 and 0.1 g/mL, respectively. The intra-day assay precision values (coefficients of variation) were generally low, in the ranges of 3.69–5.88% and 4.21–6.18% for rat plasma and urine, respectively; the corresponding inter-day assay precision values were 5.06 and 5.46%, also respectively. The accuracies (relative errors) ranged from 89.5 to 111%. No interference from endogenous substances was found. An initial pharmacokinetic study was performed in Sprague-Dawley rats and demonstrated that tofacitinib has a short half-life (39.0 min) and wide tissue distribution. In summary, this HPLC method can be applied to future preclinical and clinical investigations of tofacitinib.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/19255
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Special Graduate Schools > Graduate School of Clinical Pharmacy and Pharmaceutics > Department of Clinical Pharmacy and Pharmaceutics > 3. Theses(Master)
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