替米沙坦片血药浓度的HPLC测定方法及其在健康人体的药动学研究

目的: 建立高效液相色谱法测定人血浆中替米沙坦的药物浓度,并研究其在健康人体内的药动学3方法: 采用高效液相色谱-焚光检测法,色谱柱为 Hypersil C₁₈柱(250 mm×4.6 mm,5 μm);流动相为乙腈-磷酸盐缓冲液（45:55,pH 5.8);流速为1.0 ml·min^-1;激发波长和发射波长分别为305 nm和365 nm;进样量20 μl;内标物为α-萘酚。结果: 替米沙坦在2~1 024 μg·L^-1范围内线性良好（r=0.9999),回收率,日间、日内差均符合生物样品分析要求。10名健康受试者口服替米沙坦片80 mg后的药动学结果表明,其体内过程符合二房室开放模型,主要药动学参数如下:C_max为0.98±0.44 mg·L^-1;T_max为 0.83±0.45 h; t_1/2为 1.67±1.26 h; t_1/2β为26.00±14.43 h;t_1/2kd为 0.53±0.86h;AUC_0-l为 3.66±2.10 mg·h ^-1; AUC_0-∞为 3.98±2.40 mg·h ^-1·L ^-1。 结论: 此方法便捷,准确,灵敏,适于替米沙坦血药浓度测定和药动学研究,本试验所得药动学参数可为临床合理用药提供理论依据。

Pharmacokinetics of telmisartan tablets in healthy volunteers by HPLC

AIM: To establish an HPLC-fluorimetric method in determination of the concentrations of telmisar-tan in plasma of healthy volunteers and to investigate its pharmacokinetics. METHODS: The chromatographic column was Hypersil C18 column (250 mm×4.6 mm,5 μm). The mobile phase was acetonitrile-pH 5.8 phos-phate buffer (45:55) and the flow rate was 1.0 ml·min^-1. The fluorimetric excitation and emission wave-lengths were set at 305 nm and 365 nm, respectively. The internal standard was a~naphthol. Blood samples were deproteined by adding acetonitrile. The injection volume was 20 μl. RESULTS: The linearity correlation of telm-isartan ranged from 2 to 1 024 μg·L^-1 (r=0.9999) and the precision and stability of the method were fine. The pharmacokinetics of telmisartan was studied in healthy volunteers after oral administration of 80 mg telmisaitan tablets. It showed that the c-t curves of telmisartan con-formed to the two-compartment open model. The main pharmacokinetic parameters of telmisartan were as follows: C_max 0.98±0.44 mg·L^-1; mg·L^-10.83±0.45 h, t_1/2α 1.67±1.26 h, t_1/2β26.00±14.43 h,t_1/2ka0.53±0.86 h,AUC_0-l 3.66±2.10 mg·h ^-1·L ^-1,and AUC_0-∞ 3.98±2.40 mg·h ^-1·L ^-1. CONCLUSION: This is a convenient, sensitive, accurate and reproducible method for determining the concentrations of telmisartan in plasma of healthy volunteers and investigating its pliarma-cokinetics.