液相色谱串联质谱法测定人血浆中文拉法辛及其代谢物的浓度  

Determination of venlafaxine and its metabolite O-desmethylvenlafaxine in human plasma by LC-MS/MS method

作　　者：陆川 刘罡一 茅晓寅 贾晶莹 张梦琪 刘艳梅 余琛 

机构地区：[1]徐汇区中心医院中心实验室,上海200031 [2]上海医药临床研究中心分析化学部,上海200233

出　　处：《中国新药与临床杂志》2011年第8期634-638,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：上海市科委科研计划项目(08411966700)

摘　　要：目的建立测定血浆中文拉法辛及其代谢物O-去甲基文拉法辛的液相色谱串联质谱(LC-MS/MS)方法。方法血浆样品中加入内标(氘6-文拉法辛和氘6-O-去甲基文拉法辛),直接沉淀法处理样品。色谱柱为CAPCELL PAK C18 MGⅢ分析柱(100 mm×2.0 mm,5μm),流动相为含0.3%甲酸的水溶液-含0.3%甲酸的乙腈溶液(78∶22,V/V),流速为0.3 mL.min-1。正离子多离子反应监测(MRM)扫描分析,离子通道分别为m/z 278→58(文拉法辛)、m/z 264→58(O-去甲基文拉法辛)、m/z 284→58(氘6-文拉法辛)、m/z 270→58(氘6-O-去甲基文拉法辛)。结果文拉法辛和O-去甲基文拉法辛的线性范围均为2～1 000μg.L-1,定量下限均为2μg.L-1,提取回收率在90.14%～97.33%,批内、批间RSD均小于8%。结论本方法操作简便,特异性强,灵敏度高,可用于人血浆内文拉法辛和O-去甲基文拉法辛的含量测定研究。AIM To establish a LC-MS/MS method for the determination of venlafaxine and O- desmethylvenlafaxine in human plasma. METHODS After addition of venlafaxine-D6 （internal standard, IS） and O-desmethylvenlafaxine-D6 （IS）combination, the analyte was processed by protein precipitation. The chromatographic separation was performed on CAPCELL PAK C18 MG Ⅲ（100 mm× 2.0 mm, 5μm） column with a mobile phase of 0.3% formic acid water-0.3% formic acid acetonitrile （78 ： 22, V/V） at a flow rate of 0.3 mL·min-1. The protonated ions of analytes were detected in positive ionization by multiple reaction monitoring mode （MRM）. The mass transition pairs of m/z 278→58, m/z 264→58 and m/z 284→58, m/z 270→58 were used to detect venlafaxine, venlafaxine-D6 and O-desmethylvenlafaxine, O-desmethylvenlafaxine-D6, respectively. RESULTS The linear concentration range for venlafaxine and O-desmethylvenlafaxine were both 2 - 1 000μg·L-1. The limit of quantitation for both was 2 μg·L-1. The extraction recovery was 90.14% - 97.33%. Within-batch RSD and between-batch RSD were less than 8%. CONCLUSION This method is simple, specific and sensitive, and suitable for determination studies of venlafaxine and O-desmethylvenlafaxine in human plasma.

关 键 词：文拉法辛 O-去甲基文拉法辛 色谱法 高压液相 串联质谱法 血浆 

分 类 号：R971.43[医药卫生—药品] R927.2[医药卫生—药学]