LC-MS／MS法测定人血浆中氯沙坦及其代谢物E-3174的浓度

目的建立LC-MS／MS法测定人血浆中氯沙坦及其代谢物E-3174血药浓度的方法。方法血浆酸化后用乙醚提取，采用同位素内标（氘3-B3174）进行测定。色谱柱：CAPCELLPACKC18Ⅲ（100mm×2．0mm，5μm），流动相：0．02％甲酸乙腈-水溶液（53：47，v／v）；等度洗脱；流速0．3mL·min-1；进样体积5μL；电喷雾离子化，正离子MRM扫描。结果氯沙坦和E-3174线性范围均为5—500μg·L-1（r〉0．999），最低定量限均为5μg·L-1，平均提取回收率均〉50％，批内、批间精密度RSD均〈8％。结论本方法灵敏度高、专一性好、操作简单，适用于氯沙坦的药动学研究。

Simultaneous determination of losartan and its active metabolite E-3174 in human plasma by liquid chromatography tandem mass spectrometry method

AIM To develop a LC-MS/MS method for the determination of losartan and its active metabolite E- 3174 in human plasma. METHODS The plasma samples were extracted with ethyl ether after acidification and isotope-labeled internal standards （Losartan-d3 carboxylic acid, IS） was used. The analytical column was CAPCELL PACK C18 Ⅲ （100 mm×2.0 mm,5 μm）. The mobile phase consisted of 0.02% formic acid acetonitrile and water（53：47, V/V）, and the flow rate was 0.3 mL·min-1. The injection volume was 5μL. The protonated ions of analytes were detected in positive ionization by multiple reaction monitoring （MRM） mode. RESULTS The assay was vahdated from 5 to 500 μg·L-1（ r 〉 0.999）in plasma for losartan and E-3174. The lower lirrdt of quantitation was both 5 μg·L-1 The extraction recovery was more than 50%. The intra- and inter-batch precisions （RSD） were all less than 8%. CONCLUSION The established LC-MS/MS method is shown to be sensitive, accurate, simple and suitable for the pharmacokinetic research of losartan.