关键词: 氟桂利嗪, LC-MS/MS, 药代动力学

Abstract: AIM: To establish a LC-MS/MS method for determination of flunarizine in human plasma, and to study the relative bioequivalence of flunarizine hydrochloride made by Yangtze River Pharmaceutical Group Co., Ltd. METHODS: Thermo Hypurity C₁₈ column (150 mm×2.1 mm, 5 μm) was used in the experiment.Acetonitrile-10 mmol/L ammonium formate (including 0.1% formic acid) (65∶35, V/V) was used as mobile phase and the flow rate was 0.3 mL/min and the injection volume was 10 μL.The column temperature was set at 40 ℃,the sample room temperature was set at 15℃.A single oral dose of 20 mg flunarizine hydrochloride and its contrastive drug were given to 18 healthy volunteers in an open randomized two way crossover design.The plasma concentrations were determined by LC-MS/MS method at the different time points. RESULTS: Flunarizine was linear in the range of 0.38-196 ng/mL, the limitation of detection for flunarizine was 0.1 ng/mL,the method was high sensitivity, stability and specificity. The main pharmacokinetic parameters of flunarizine were as follows: C_max was (86±36) and (82±34 )ng/mL;t_max was 2.5 h(1-3 h) and 3 h(2-5 h);AUC_0-24 was (725±338) and (709±320) ng·mL^-1·h;AUC_0-∞ was (811±375) and (780±330) ng·mL^-1·h.The reference drug and the test drug of flunarizine are bioequivalent. CONCLUSION: The method is simple, accurate and repetitive for the determination of flunarizine in human plasma and successfully applied to the bioequivalence evaluation of flunarizine hydrochloride in human.

Key words: Flunarizine, LC-MS/MS, Pharmacokinetics