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目的建立用于测定人血浆中复方替米沙坦片中两种成分替米沙坦和氢氯噻嗪的HPLC测定方法,并用于研究健康志愿者口服复方替米沙坦片的药动学特征。方法 12名健康志愿者口服试验片剂,于规定时间点取血,分别用高效液相-荧光法和高效液相-二级质谱联用测定人血浆中替米沙坦和氢氯噻嗪浓度。用梯形法计算AUC,以实测值计算t_(max)和ρ_(max),采用药动学统计软件DAS2.0计算其他药动学参数。结果替米沙坦的线性范围为2.5～500μg·L~(-1),r=0.999 9,方法回收率99.42%～108.69%,RSD均≤2.62%,最低检测浓度为1.25μg·L~(-1);氢氯噻嗪的线性范围为1～200μg·L~(-1)(r=0.999 4),方法回收率95.58%～112.15%,RSD均≤4.86%,最低检测浓度为0.5μg·L~(-1)。12名受试者口服复方替米沙坦后,替米沙坦的主要药动学参数为:AUC_(0→t)(1 800±859)μg·h·L~(-1),AUC_(0→∞)(1 967±858)μg·h·L~(-1),ρ_(max)(181±68)μg·L~(-1),t_(max)(1.7±0.9)h,t_(1/2)(22.15±10.64)h。氢氯噻嗪的主要药动学参数为AUC_(0→t)(519±151)μg·h·L~(-1),AUC_(0→∞)(542±149)μg·h·L~(-1),ρ_(max)(72.3±25.1)μg·L~(-1),t_(max)(2.3±0.9)h,t_(1/2)(7.44±2.50)h。结论建立的替米沙坦和氢氯噻嗪的HPLC测定方法灵敏、准确、专属,适合于复方制剂两成分的血药浓度测定。体内药动学研究表明该复方制剂两成分没有改变各自体内的药动学行为。
OBJECTIVE To establish a HPLC method for the determination of telmisartan and hydrochlorothiazide in compound plasma telmisartan tablets in human plasma and to study the pharmacokinetics of oral telmisartan tablets in healthy volunteers. Methods Twenty healthy volunteers were orally administered with the tablets and blood was taken at the prescribed time points. The concentrations of telmisartan and hydrochlorothiazide in human plasma were determined by HPLC - HPLC and HPLC - MS respectively. Trapezoidal method was used to calculate AUC, t_ (max) and ρ_ (max) were calculated and the other pharmacokinetic parameters were calculated using pharmacokinetic statistics software DAS2.0. Results The linear range of telmisartan was 2.5-500μg · L -1, r = 0.999 9, the recovery rates were 99.42% -108.69%, RSDs were both ≤2.62%, and the lowest concentrations were 1.25μg · L ~ (-1) -1). The linear range of hydrochlorothiazide was 1 ~ 200μg · L -1 (r = 0.999 4). The recoveries were 95.58% ~ 112.15% with RSDs less than 4.86% and the lowest detection limit was 0.5μg · L ~ (-1). The main pharmacokinetic parameters of telmisartan in 12 subjects after oral administration of compound telmisartan were: AUC_ (0 → t) (1 800 ± 859) μg · h · L -1, AUC_ ( 0 → ∞) (1 967 ± 858) μg · h · L -1, ρ max (181 ± 68) μg · L -1, t max (1.7 ± 0.9) h, t_ (1/2) (22.15 ± 10.64) h. The main pharmacokinetic parameters of hydrochlorothiazide were AUC_ (0 → t) (519 ± 151) μg · h · L -1, AUC_ (0 → ∞) (542 ± 149) μg · h · L -1 ), ρ max (72.3 ± 25.1) μg · L -1, t max (2.3 ± 0.9) h, t 1/2 (7.44 ± 2.50) h. Conclusion The established HPLC method for the determination of telmisartan and hydrochlorothiazide is sensitive, accurate and specific, and is suitable for the determination of blood concentration in two components of compound preparations. In vivo pharmacokinetic studies have shown that the two components of the compound did not change their pharmacokinetic behavior in vivo.