LC-MS/MS法快速测定人血浆中美沙酮的浓度  

Rapid Determination of Methadone in Human Plasma by LC-MS/MS

作　　者：温预关[1] 汤健聪[2] 

机构地区：[1]广州市脑科医院/国家药品临床研究基地,广州市510370 [2]广东药学院药科学院,广州市510006

出　　处：《中国药房》2008年第32期2503-2505,共3页China Pharmacy

基　　金：广东省自然科学基金资助项目(8151037001000001);广东省医院药学研究基金资助项目(2008B001);广州市医药卫生科技基金资助项目(2007-YB-106)

摘　　要：目的:建立快速测定人血浆中美沙酮浓度的方法。方法:采用高效液相色谱串联质谱电喷雾检测(LC-MS/MS)法。色谱柱为AgilentTCC18,流动相为甲醇-5mmol·L-1甲酸铵(90∶10),流速为1mL·min-1,柱温为25℃,提取剂为醋酸乙酯∶二氯甲烷(4∶1)。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择反应监测(SRM)对美沙酮(m/z310.0→264.9)和内标地西泮(m/z285.1→154.0)进行测定。结果:美沙酮血药浓度在2.5～500μg·L-1范围内线性关系良好(r=0.9990),分析方法的最低定量限为2.5μg·L-1;其高、中、低(300、100、5μg·L-1)3种浓度的平均方法回收率分别为100.23%、101.20%和101.39%,日内(n=5)、日间(n=3)RSD均<10%。结论:本方法简单、快速、灵敏、准确、重现性好,可用于美沙酮的临床血药浓度监测和药动学研究。OBJECTIVE： To set up a LC- MS/ MS method for determination of plasma concentration of methadone. METHODS： Methadone was extracted with ethyl acetate and dichloromethane （4 ： 1） and the residues were analyzed with a LC - MS/ MS system using Agilent TC C18 column at a column temperature of 25 ℃ with the mobile phase consisted of methanol - 5 mmol · L^-1 ammonium formate （90 ： 10） at a flow rate of 1 mL·min^-1. An agilent 6410 triple quad mass spectrometer system equipped with an electrospray ionization ion - trap source was used as the detector and operated in the positive ion mode. Selected reaction monitoring （SRM） using the precursor to product ion combinations of m/z 310.0→264.9 and m/ z 285.1→154.0 was performed to detect methadone and diazepam （the internal standard）, respectively. RESULTS： The calibration curves for methadone had good linearity over the range of 2.5-500μg · L^-1（r = 0.999 0） . The limits of quantitation for methadone was 2.5 μg · L^-1. The average recoveries for methadone （at high, medium and low concentrations） were 100.23%, 101.20% and 101.39%, respectively. The within- day RSD （n = 5） and between- day RSD （n = 3） were all less than 10%. CONCLUSION： The method is simple, rapid, sensitive, accurate, and reproducible and it provides an analytical procedure for clinical monitoring of plasma concentration of methadone and its pharmacokinetic studies.

关 键 词：美沙酮 血药浓度 高效液相色谱串联质谱电喷雾法 

分 类 号：R969.1[医药卫生—药理学]