HPLC-荧光检测法测定人血浆中替米沙坦的质量浓度及药代动力学研究

Determination of telmisartan in human plasma by HPLC with fluorimetric detection and study on its pharmacokinetics

目的建立人血浆中替米沙坦质量浓度的HPLC-荧光检测法，测定健康受试者口服替米沙坦片后的血药浓度，并计算其药代动力学参数。方法18名男性健康受试者单剂量口服替米沙坦80mg，血浆经过简单处理，用荧光检测器RP-HPLC法测定。采用C18（250mm×4．6mm，5μm）色谱柱，流动相：0．1％醋酸铵-乙腈（40：60），冰醋酸调pH6．5。流速1．0mL·min^-1，荧光检测激发波长315nm，发射波长365nm。结果替米沙坦的线性范围为2．5～750ng·mL^-1（r=0．9998），最低检测浓度为0．5ng·mL^-1，达峰时间Tmax为（1．23±0．37）h；血药浓度峰值Cmax为（485．16±219．28）ng·mL^-1；T1/2β为（17．24±3．91）h；药时曲线下面积AUC（0→48）为（2645．41±1069．74）ng·h·mL^-1。结论该法简单、灵敏、准确，可用于替米沙坦的体内分析。

Objective To establish an HPLC -fluorescence method for quantitative determination of telmisartan in human plasma and to study the pharmacokinetics characteristics of telmisartan tablets in human. Methods 18 male healthy volunteers orally took a single dose of 80 mg tablets. The plasma concentrations of telmisartan were determined by RP-HPLC with fluorescent detector. The determination has been performed on a C18 column （ 250 mm× 4.6 mm,5 μm） with acetonitrile-0. 1% NH4Ac（40 ： 60） as mobile phase adjusted pH to 6.5 . The flow rate was 1.0 mL · min^-1. The fluorimetric excitation and emission wavelength were set at 315 nm and 365 nm. Results The calibration curve for telmisartan was linear in the range of 2.5 to 750 ng · mL^-1 （ r =0. 999 8）. The limit of quantitation for telmisartan was 0.5 ng · mL^-1. The pharmacokinetic parameters were as follow ： T max （1.23-1-0.37） h; Cmax （485.16±219.28） ng ·mL^-1; T1/2β （17.24±3.91） h; AUC（0→48） 2 645.41±1 069.74 ng ·h·mL^-1 ,respectively. Conclusion The method provides a simple, sensitive, accurate and reliable procedure for determination of telmisartan in plasma.