HPLC-RIF法研究罗格列酮在中国2型糖尿病患者体内的多剂量药动学特点

Study HPLC-RIF on multiple -dose pharmacokinetics of rosiglitazone in Chinese patients with type 2 diabetes

目的:建立RP-HPLC-RIF法测定人血浆中罗格列酮(RSG)的浓度,并研究RSG在中国2型糖尿病患者体内的多剂量药物动力学。方法:血样经乙腈沉淀蛋白后进样分析,用MACHEREY-NAGEL NUCLEODUR C_(18)柱(250mm×4.6mm,5μm),柱温50℃,流动相为乙腈和30mmol·L^(-1)醋酸铵(含0.1%甲酸),流速为1mL·min^(-1),采用梯度洗脱程序和时间程序测定,用非房室模型法分析RSG血药浓度-时间数据。结果:RSG在2.29～431.40μg·L^(-1)浓度范围内线性良好,最低定量限为2.29μg·L^(-1)。萃取回收率均大于90%,方法回收率在98.5%～101.3%之间,日内RSD均小于10.0%,日间RSD小于16.0%。RSG多剂量给药的主要药动学参数T_(max)为(2.1±1.8)h,C_(max)^(ss)为(310.0±132.1)μg·L^(-1),C_(min)^(ss)为(56.8±31.5)μg·L^(-1),AUC_(0-∞)^(ss)为(2517.3±919.0)μg·h·L^(-1),t_(1/2)为(4.6±2.2)h,CL/F为(2.5±0.7)L·h^(-1),V_(ss)/F为(16.5±9.5)L,MRT_(0-∞)为(9.6±3.0)h,DF为(170.0±60.0)%。结论:该法样品处理简便、方法准确可靠,适合RSG在中国2型糖尿病患者体内的药物动力学研究。RSG在中国2型糖尿病患者体内吸收迅速,分布广泛,消除快,且能被患者耐受。

Objective： To build a RP- HPLC -RIF method to determine the concentration of rosiglitazone（RSG） in human plasma and study its multiple - dose pharmacokinetics in patients with type 2 diabetes. Methods： Blood samples were injected after protein being precipitated, by acetonitrile, RSG was separated on MACHEREY - NAGEL NUCLEODUR C18 column（250 mm × 4. 6 mm,5 μm）at 50 ℃ using gradient eluting procedure and time program. Mobile phase was constituted of acetonitrile and 30 mmol· L^-1ammonium acetate （ including 0. 1% formic acid）, the flow rate was 1 mL·min^-1. The pharmacokinetic parameters were generated using noncompartmental methods. Results. The linear range was 2. 29 - 431.40 μg ·L ^-1, the LOQ was 2. 29 μg · L^-1 . Extraction recoveries of RSG were more than 90% ,relative recoveries were 98. 5% - 101.3%. Intra -day RSD were less than 10% ,inter -day RSD were less than 16%. The main parameters： Tmax（2. 1 ± 1.8）h,Cmax^ss（310. 0 ± 132. 1） μg · L^-1,Cmin^ss（56.8 ± 31.5）μg·L^-1,AUC0-∞^ss（2517.3±919.0）μg·h· L^-1,t1/2（4.6±2.2）h,CL/F（2.5±0.7）L·h^-1,Vss/F （ 16. 5±9.5 ） L, MRT0-∞ （ 9.6±3.0） h, DF （ 170. 0 ± 60.0） %. Condusion： The method is simple, sensitive, accurate. It can be used to study pharmacokinetics of RSG in patients with type 2 diabetes. RSG is absorbed quickly, distributed widely and metabolized lastly. It can be tolerated by participants well.