离子对高效液相色谱法测定人血浆中氢氯噻嗪浓度及药动学

Determination of hydrochlorothiazide and its pharmacokinetics in human plasma by iron-pair HPLC

目的：建立离子对高效液相色谱法测定人血浆中的氢氯噻嗪（HCTZ）浓度，研究人体的药动学。方法：采用C18柱，以乙腈-0．15％辛磺酸钠（17：83）为流动相，紫外检测波长272nm。血浆样品用甲基叔丁基醚提取吹干浓缩后进样。对10名健康志愿者口服氢氯噻嗪片25mg后不同时间的血药浓度进行测定。结果：平均回收率大于95．0％，日间和日内RSD小于15．0％，血浆最低检测限3.8μg·L^-1，线性范围3．8～380．0μg·L^-1。主要药动学参数t1／2、Cmax、tmax、AUC0-36、AUC0-∞分别为：（9．6±2．6）h，（156、1±60．9）μg·L^-1，（1．4±0．4）h，（1236.3±346．9）μg·h·L^-1，（1347.3±327．8）μg·h·L^-1。结论：方法能满足HCTZ血药浓度监测和药动学研究的需要。

OBJECTIVE To determine concentration of hydrochlorothiazide （HCTZ） in human plasma with iron-pair HPLC, and study pharmacokinetics of the drug following a single oral dose in healthy volunteers. METHODS A C18 column was used, and the mo- bile phase consisted of acetonitrile - 0.15% octanesulfonate sodium（ 17：83 ）, and detected at 272 nm. Hydrochlorothiazide in plasma sample was extracted by methyl tert-butyl ether. RESULTS The mean recovery was more than 95.0%, and the intra, inter day RSDs were less than 15.0%, the detection limit was 3.8 μg·L^-1, the linear range was 3.8 -380.0 μg·L^-1. The pharmacokinetic parameter t1/2, Cmax AUC0-36, AUC0-∞ was （9.6 ±2.6） h, （ 156.1 ±60.9）μg · L^-1, （ 1.4 ±0.4） h, （ 1 236.3 ±346.9） μg · h · L^-1, （1 347.3 ±327.8） μg·h· L^-1 in ten healthy volunteers after oral administration of 25 mg HCTZ, respectively. CONCLUSION The method is suitable for the determination of HCTZ concentration in human plasma and for the study of pharmacokinetics.