AJOU Central Library Repository: 혈장, 뇨 및 조직 중 JAK 억제제인 tofacitinib의 HPLC분석법 및 약물동력학 연구에의 적용

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

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.

Appears in Collections:: Special Graduate Schools > Graduate School of Clinical Pharmacy and Pharmaceutics > Department of Clinical Pharmacy and Pharmaceutics > 3. Theses(Master)

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