LC-ESI-MS法测定人血浆中愈创木酚甘油醚的浓度及在药动学中的应用___

目的:建立LC-ESI-MS法测定人血浆中愈创木酚甘油醚的浓度，明确其在人体中的药代动力学特征。方法：血浆样品采用乙酸乙酯液-液萃取法处理，取上清液进样。以甲醇-水（43∶57，v/v，含0.4%乙酸和0.4 mmol•mL-1乙酸胺）为流动相 用Shimadzu Pack VP-ODS C18 （5 μm，150 mm×2.0 mm）色谱柱分离 以罗红霉素为内标。流速0.2 mL•min-1 柱温35 ℃ 进样量10 μL。采用电喷雾电离源（ESI），选择性监测愈创木酚甘油醚（m/z 199.0），内标罗红霉素（m/z 837.5）。结果：愈创木酚甘油醚的线性范围为25.0~6400.0 ng•mL-1，线性关系良好(r=0.9999)，最低定量下限为25.0 ng•mL-1，绝对回收率大于85%，批间和批内的变异系数小于15%。结论：该方法预处理快速简单，灵敏度高，可用于愈创木酚甘油醚的药动学研究及临床血药浓度监测。

Objective:To establish an LC-ESI-MS method for determination of guaifenesinum in human plasma and study the pharmacokinetics characteristics of it in healthy volunteers.Methods:The plasma samples were pretreated with liquid-liquid extraction in ethyl acetate.Samples were analyzed on Shimadzu Pack VP-ODS C18( 5 μm,150 mm×2.0 mm ) column,the mobile phase consisting of methanol-water(43∶57) containing 0.4% glacial acetic acid and 0.4 mmol•mL-1 ammonium acetate,the flow rate was 0.2 mL•min-1 column temperature was set at 35 ℃.The volume of injection was 10 μL.The analyte and internal standard Roxithromycin were both analyzed by MS in the ESI,m/z was 199.0 for guaifenesinum and 837.5 for the IS,respectively.Results:The method was linear in the concentration range of 25.0-6400.0 ng•mL-1 (r=0.9999),the absolute recovery was greater than 85%.The within-run and between-run relative standard deviation was less than 15%.Conclusion:This method is easy,sensitive,therefore,it can be used to analyze human plasma samples for application in pharmacokinetic studies and clinical therapeutic drug monitoring.

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