LC-MS法测定人血浆中格列苯脲及其在健康志愿者中的药代动力学

Determination of Glibenclamide in Human Plasma by LC-MS and Study of Its Pharmacokinetics in Healthy Chinese Volunteers

目的测定人血浆中格列苯脲的浓度,并研究在中国志愿者中单剂量口服5mg后的药代动力学过程。方法用液液萃取法提取血浆中药物。采用液相色谱质谱联用的分析手段,建立人血浆中格列苯脲浓度的测定方法。结果格列苯脲在156～400μg/L浓度范围内线性良好(r=09999),其在人血浆中的回收率大于80%,日内、日间RSD分别为36%～68%和61%～84%。最低检测限为05ng/ml。该药在人体内的主要动力学参数为AUC0∞=(8136±2542)μg·h/L,AUC0t=(7906±2482)μg·h/L,cmax=(1301±648)ng/ml,tmax=(26±18)h和t1/2=(27±19)h。结论本方法专属性强,灵敏度高,可准确测定格列苯脲在人血浆中的浓度。

AIM:To determine the concentration of glibenclamide in human plasma and investigate its pharmacokinetics in Chinese male volunteers following oral administration of a single dose of 5mg.METHOD:Plasma samples were processed by liquid-liquid extraction and a high-performance liquid chromatographic-electrospray ionization mass spectroscopy(HPLC-ESI-MS) for determination of intact glibenclamide in human plasma has been developed.RESULT:The method was linear in the 1.56～400 ng/ml concentration range(r=0.9999).The recovery of glibenclamide was more than 80%.Within-day and between-day precision,expressed as the relative standard deviation(RSD),ranged from 3.6% to 6.8% and 6.1% to 8.4% respectively.The sensitivity of the method was 0.5 ng/ml.The assay was used to estimate the pharmacokinetics of glibenclamide after oral administration of a 5mg tablet of glibenclamide to 18 healthy volunteers.Its main pharmacokinetic parameters were:AUC 0-∞ =(813.6±254.2) μg·h/L,AUC 0-t =(790.6±248.2) μg·h/L,c max =(130.1±64.8) ng/ml,t max =(2.6±1.8) h and t 1/2 =(2.7±1.9) h.CONCLUSION:The method described in this report has high sensitivity and selectivity for accurate determination of the human plasma concentration of glibenclamide.