米索前列醇片在健康人体内的药动学特征

Pharmacokinetic characteristics of misoprostol tablets in healthy volunteers

目的建立人血浆中米索前列醇浓度的LC-MS/MS检测方法,研究米索前列醇片在健康志愿者体内的药动学特征。方法采用K-MS/MS C_(18)分析色谱柱(150 mm×4.6 mm,5μm);流动相为甲醇-水-1%氨水(55:45:0.075,V/V/V);流速为0.5 mL·min^(-1);柱温为室温。结果该测定方法的线性范围为10～3000 ng·L^(-1)(r=0.9964),最低检测浓度为10.0 ng·L^(-1)(按R_(S,N)≥3计),提取回收率为80%～90%,日内和日间RSD均<10%。药动学研究表明,米索前列醇片在体内代谢过程符合一室模型,主要药动学参数t_(1/2)、ρ_(max)、t_(max)、AUC_(0-360)分别为:(1.15±0.26)h,(1 209±973)ng·L^(-1),(32±13)min,(1 359±1 015)ng·h·L^(-1)。结论本法具有良好的准确性和较高的灵敏度,简便快速,适用于米索前列醇片血药浓度的测定和药动学研究。

A/M To establish LC-MS/MS method for detection of misoprostol in human plasma and to study the pharmacokinetic characteristics of misoprostol tablets in healthy volunteers. METHODS LC-MS/MS analysis was performed using a Zorbax SB column （ 150 mm × 4.6 mm, 5μm） ; The mobile phase consisted of acetonitrile-water-ammonia （55：45：0.075, V/V/V）. The flowrate was 0.5 mL·min^-1 and the temperature of column was about 27℃. RESULTS The linear calibration curve of misoprostol in plasma was obtained over the range of 10 - 3 000 ng· L^- 1 （ r = 0.996 4）. The minimal detectable drag concentration was 10.0 ng· L^- 1 （ RS,N ≥ 3）. The average recovery rate was 80% - 90%. The inter-day and intra-day validation were less than 10%. The main pharmacokinetic parameters of misoprostol tables were as follows： t1/2 （1.15 ± 0.26） h; ρmax （1 209 ± 973）ng· L^-1; tmax （32 ± 13）min; AUC0→360 （1 359 ± 1 015）ng· h· L^-1, which were fitted to one-compartment model. CONCLUSION The method is accurate, sensitive, simple, and rapid, and could be used for blood concentration monitoring and pharmacokinetic study, which may be the basis of clinically reasonable drug-taking.