LC/MS/MS法测定血浆、羊水中曲马多及其活性代谢物氧去甲基曲马多  

Determination of tramadol and its active metabolite O-desmethyltramadol in plasma and amniotic fluid using LC/MS/MS

作　　者：肇丽梅[1] 陈笑艳[2] 崔健君[3] SUNITA Maleku 钟大放[2] 

机构地区：[1]中国医科大学附属第二医院临床药理研究室,辽宁沈阳110004 [2]沈阳药科大学药物代谢与药物动力学实验室,辽宁沈阳110016 [3]中国医科大学附属第二医院麻醉科,辽宁沈阳110004

出　　处：《药学学报》2004年第6期458-462,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 3 993 0 180 )

摘　　要：目的　建立液相色谱 串联质谱法 (LC MS MS)同时测定血浆和羊水中曲马多和氧去甲基曲马多 ,并研究其在母体和胎儿体内分布。方法　生物样本经液 液提取 ,通过液相色谱 -串联质谱 ,以选择离子反应监测 (SRM)方式进行检测。结果　测定血浆样品曲马多和氧去甲基曲马多的线性范围为 8 0 80 0 0 μg·L- 1 ;测定羊水样品曲马多和氧去甲基曲马多的线性范围为 1 0 4 0 0 0 μg·L- 1 。 1 2例剖宫产产妇术前im盐酸曲马多 (1 5mg·kg- 1 )后 ,血浆中曲马多和氧去甲基曲马多浓度较高 ,羊水中曲马多浓度较低 ,且未检测出氧去甲基曲马多。结论　本方法操作简便、灵敏度高 。Aim To determinate tramadol and O desmethyltramadol in human plasma and amniotic fluid by LC/MS/MS, and distribution of tramadol and O desmethyltramadol in maternity and fetus were studied. Methods Samples containing tramadol, O desmethyltramadol and diphenhydramine (internal standard, IS ) were extracted using liquid liquid extraction, followed by liquid chromatographic separation and on line MS/MS using atmospheric pressure chemical ionization as an interface detection. The analytes were detected in the selected reaction monitoring mode. Results The calibration curves for tramadol and O desmethytramadol in plasma and amniotic fluid were linear in the range from 8 0 to 800 0 μg·L -1 (plasma) and 1 0 to 400 0 μg·L -1 (amniotic fluid). The method was applied to the measurement of tramadol and O desmethytramadol concentrations in maternal vein, umbilical vein, umbilical artery and amniotic fluid. Following intramuscular pre operative administration 1 5 mg·kg -1 doses of tramadol to parturients, plasma concentrations of tramadol were significantly higher than those in amniotic fluid. The concentrations of O desmethyltramadol in plasma were lower, and were not detected in amniotic fluid. Conclusion The method is shown to be accurate, robust and convenient, and suitable for clinical pharmacokinetics studies of tramadol and O desmethyltramadol.

关 键 词：LC/MS/MS法 测定 血浆 羊水 曲马多 活性代谢物 氧去甲基曲马多 液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学]