HPLC-MS测定人血浆中多沙唑嗪及其在健康人体药动学研究中的应用

HPLC-MS determination of doxazosin in the human plasma and its pharmacokinetics

目的:建立人血浆中多沙唑嗪的高效液相色谱-质谱测定方法,用于研究甲磺酸多沙唑嗪片的健康人体药动学。方法:血浆样品0.25 mL,用正己烷-叔丁基甲醚萃取,以20 mmol·L^(-1)醋酸铵溶液(pH 4.28)-甲醇-乙腈(55:10:35)为流动相,用 Thermo C_(18)柱(150 mm×2.1 mm,5μm)分离,采用高效液相色谱-质谱电喷雾电离法,选择离子监测(SIM)。测定12名健康男性志愿者单剂量口服4 mg 甲磺酸多沙唑嗪片后的血药浓度经时过程。由 DAS2.0药学与统计程序处理计算药动学参数。结果:多沙唑嗪的线性范围为0.5～100 ng·mL^(-1),平均回收率为98.3%,日内 RSD≤8.4%,日间 RSD≤10.5%。结论:分析方法准确、灵敏度高,适用于多沙唑嗪口服制剂的药动学研究。

Objective：To determine doxazosin in human plasma by HPLC -MS method, and to study its pharmacokinetic in healthy volunteers. Methods： Doxazosin concentration in plasma was determined by HPLC - MS. Doxazosin was extracted from plasma with liquid -liquid extraction, and then separated on a Thermo C 18 column（ 150 mm × 2. 1 mm ,5 μm）. The mobile phase consisted of 20 mmol · L^-1ammonium acetate（ pH 4. 28 ） -methanol- acetonitrile（55： 10： 35 ） ;the selected ion was determined by ESI ^＋ ;The pharmacokinetic parameters were obtained with the help of DAS2. 0 System. Results：The calibration curve was linear within the range of 0. 5 - 100 ng · mL^-1 （r = 0. 9988 ） ,the recovery was 98.3% ,the RSDs of intra - and inter -day were less than 8.4% and 10. 5%. Conclusion：The method is rapid and sensitive. Pharmacokinetic parameters are consistent with the literature report.