HPLC法测定人血浆中的氢氯噻嗪及其在药代动力学研究中的应用

Determination of hydrochlorothiazide in human plasma and pharmacokinetic study by HPLC

目的以氟康唑为内标(IS),建立一种测定人血浆中氢氯噻嗪的HPLC法,研究氢氯噻嗪在人体内的药动学。方法选取20名男性健康志愿者,单剂量口服氢氯噻嗪片50mg后0.5~36h内间隔采集肘静脉血,分离血浆,测定氢氯噻嗪的血药质量浓度,计算其药代动力学参数。结果氢氯噻嗪质量浓度在5~400ng·mL^(-1)范围内线性关系良好;精密度和准确度结果表明,该方法的日内日间变异均低于9%,在低、中、高3个质量浓度下的提取回收率均大于80%;主要药动学参数分别为C_(max)=275.33±38.30ng·mL^(-1),t_(1/2)=11.70±1.60h,t_(max)=2.25±0.34h,AUC_(0→36)=2 295.75±219.15ng·mL^(-1)·h,AUC_(0→∞)=2 546.99±229.78ng·mL^(-1)·h。结论建立的方法选择性好、灵敏度高、简单快捷,可用于临床氢氯噻嗪片的血药质量浓度测定及体内药代动力学研究。

Objective To establish a high performance liquid chromatography （HPLC） method for the determination of hydrochlorothiazide （HCT） in human plasma samples using fluconazole as an internal standard （IS） and study the pharmacokinetics of Hydrochlorothiazide Tablets in healthy male Chinese volunteers. Methods 20 healthy male Chinese volunteers were given a single oral dose of 50 mg Hydrochlorothiazide Tablets.Venous blood samples were taken at predetermined time intervals between 0.5 and 36 h.The plasma was separated and the concentrations of hydrochlorothiazide were determined by the validated HPLC method and the pharmacokinetic parameters were also calculated. Results The main pharmacokinetic parameters found for hydrochlorothiazide were as follows： C max =275.33±38.30 ng·mL^ -1,t 1/2 =11.70±1.60 h,t max =2.25±0.34 h,AUC 0→36 =2 295.75±219.15 ng·mL^-1·h and AUC 0→∞ =2 546.99±229.78 ng·mL^-1·h. Conclusion The established HPLC method is sensitive,accurate,simple and suitable for the determination of hydrochlorothiazide in human plasma samples and studying pharmacokinetics of Hydrochlorothiazide Tablets.