柱前衍生化LC-MS／MS法同时测定人血浆中厄多司坦及其活性代谢物  

Simultaneous determination of erdosteine and its active metabolite in human plasma by liquid chromatography-tandem mass spectrometry with pre-column derivatization

作　　者：金经[1,2] 陈笑艳[2] 张逸凡[2] 马智宇[2] 钟大放[1,2] 

机构地区：[1]苏州大学,江苏苏州215123 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2013年第3期395-400,共6页Acta Pharmaceutica Sinica

摘　　要：建立快速、灵敏、准确的柱前衍生化液相色谱串联质谱(LC-MS/MS)法同时测定人血浆中厄多司坦及其含巯基活性代谢物,并将其应用于厄多司坦片人体药动学研究。厄多司坦及其活性代谢物分别以对乙酰氨基酚和卡托普利为内标。100μL血浆样品经2-溴-3'-甲氧基苯乙酮衍生化处理后以甲醇(含0.1%甲酸)-5 mmol.L 1醋酸铵(含0.1%甲酸)为流动相梯度洗脱,Agilent XDB-C18色谱柱(50 mm×4.6 mm ID,1.8μm)分离。采用电喷雾电离源,多反应监测方式进行正离子检测。测定人血浆中厄多司坦及其活性代谢物的标准曲线线性范围分别为5～3 000 ng.mL 1和5～10 000 ng.mL 1,定量下限均为5.00 ng.mL 1。厄多司坦片人体药动学研究发现,含巯基活性代谢物曲线下面积(AUC)是原形药物的6.2倍,平均滞留时间(MRT)为(7.51±0.788)h,为合理制订给药方案提供了药动学依据。A sensitive, rapid and accurate liquid chromatography-tandem mass spectrometric （LC-MS/MS） method with pre-column derivatization was developed for the simultaneous determination of erdosteine and its thiol-containing active metabolite in human plasma. Paracetamol and captopril were chosen as the internal standard of erdosteine and its active metabolite, respectively. Aliquots of 100 p,L plasma sample were derivatized by 2-bromine-3＇-methoxy acetophenone, then separated on an Agilent XDB-C 18 （50 mm x 4.6 mm ID, 1.8 μm） column using 0.1% formic acid methanol - 0.1% formic acid 5 mmol.L 1 ammonium acetate as mobile phase, in a gradient mode. Detection of erdosteine and its active metabolite were achieved by ESI MS/MS in the positive ion mode. The linear calibration curves for erdosteine and its active metabolite were obtained in the concentration ranges of 5-3 000 ng.mL-1 and 5-10 000 ng.mL-1, respectively. The lower limit of quantification of erdosteine and its active metabolite were both 5.00 ng.mL-1. The pharmacokinetic results of erdosteine and its thiol-containing active metabolite showed that the area under curve （AUC） of the thiol-containing active metabolite was 6.2 times of that of erdosteine after a single oral dose of 600 mg erdosteine tables in 32 healthy volunteers, The mean residence time （MRT） of the thiol-containing active metabolite was （7.51土0.788） h, which provided a pharmacokinetic basis for the rational dosage regimen.

关 键 词：液相色谱串联质谱法 厄多司坦 药动学 活性代谢物 

分 类 号：R917[医药卫生—药物分析学] R969[医药卫生—药学]