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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 rapid, sensitive and accurate pre-column derivatization liquid chromatography-tandem mass spectrometry (LC-MS / MS) method was developed for the simultaneous determination of erdosteine and its thiol-containing active metabolites in human plasma and its application to erdosteine Pharmacokinetics of tablets. Erdosteine and its active metabolites are respectively paracetamol and captopril as internal standard. 100μL plasma samples were derivatized with 2-bromo-3'-methoxyacetophenone and eluted with a mobile phase of methanol (containing 0.1% formic acid) and 5 mmol·L -1 ammonium acetate (containing 0.1% formic acid) Agilent XDB-C18 column (50 mm × 4.6 mm ID, 1.8 μm). Electrospray ionization source, multi-reaction monitoring method for positive ion detection. The linear range of the standard curve for determination of erdosteine and its active metabolite in human plasma ranged from 5 to 3 000 ng.mL 1 and from 5 to 10 000 ng.mL 1, respectively. The lower limit of quantitation was 5.00 ng.mL 1. Erdostell tablets pharmacokinetics study found that the area under the curve of active metabolites containing thiol (AUC) was 6.2 times the prototype drug, the average retention time (MRT) was (7.51 ± 0.788) h, in order to develop a reasonable dosing regimen Provided pharmacokinetic basis.