LC-MS/MS法测定血液中卡马西平及其代谢物  

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS

作　　者：崔海燕 吕晨曦 师燕华 原妮 梁嘉豪 安全[2] 郭中元 贠克明[1] CUI Hai-yan;LÜChen-xi;SHI Yan-hua;YUAN Ni;LIANG Jia-hao;AN Quan;GUO Zhong yuan;YUN Ke-ming(School of Forensic Medicine,Shanxi Medical University,Jinzhong 030600,Shanxi Province,China;China Institute for Radiation Protection,Taiyuan 030006,China;Changning Branch of Shanghai Public Secu-rity Bureau,Shanghai 200336,China)

机构地区：[1]山西医科大学法医学院,山西晋中030600 [2]中国辐射防护研究院,山西太原030006 [3]上海市公安局长宁分局,上海200336

出　　处：《法医学杂志》2023年第1期34-39,共6页Journal of Forensic Medicine

基　　金：国家自然科学基金重点资助项目(82130056);国家自然科学基金青年基金资助项目(81601647);国家博士后基金面上资助项目(2019M651086);山西省应用基础研究面上青年资助项目(201901D211332);山西省教育厅高校科技创新资助项目(2020L0191)。

摘　　要：目的建立LC-MS/MS法测定血液样品中卡马西平及其代谢物10,11-二氢-10,11-环氧卡马西平和10,11-二氢-10-羟基卡马西平的方法。方法以1-丁基-3-甲基咪唑六氟磷酸盐离子液体为萃取剂处理血液样品,通过超声辅助萃取,采用ZORBAX Eclipse Plus C18,95?色谱柱分离,流动相A为含0.1%甲酸、10 mmol/L乙酸铵的水溶液,流动相B为混合有机溶剂(V_(乙腈)∶V_(甲醇)=2∶3),梯度洗脱,流速1.00 mL/min,采用电喷雾离子源、正离子模式,多反应监测模式进行检测。结果血液样品中卡马西平及其代谢物10,11-二氢-10,11-环氧卡马西平和10,11-二氢-10-羟基卡马西平在相应范围内线性关系良好,相关系数(r)均大于0.9956,检出限分别为3.00、0.40和1.30 ng/mL,定量限分别为8.00、1.00和5.00 ng/mL,提取回收率为76.00%~106.44%,日内和日间精密度均小于16%。采用本方法从死亡案件的血液样品中检出卡马西平和主要代谢产物10,11-二氢-10,11-环氧卡马西平成分,质量浓度分别为2.71μg/mL和252.14 ng/mL。结论本方法灵敏度高、选择性好,适用于血液样品中卡马西平及其代谢物的检测,可应用于卡马西平相关的法医学鉴定。Objective To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry(LC-MS/MS).Methods The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent.The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18,95Åcolumn.The mobile phase A aqueous solution containing 0.1%formic acid and 10 mmol/L ammonium acetate,and mobile phase B mixed organic solvent containing acetonitrile/methanol(V_(acetonitrile)∶V_(methanol)=2∶3)were used for gradient elution at the flow rate of 1.00 mL/min.An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring.Results The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range,with correlation coefficients(r)greater than 0.9956.The limits of detection were 3.00,0.40 and 1.30 ng/mL,respectively.The limit of quantitation were 8.00,1.00 and 5.00 ng/mL,respectively.The extraction recoveries ranged from 76.00%to 106.44%.The relative standard deviations of the intra-day and inter-day precisions were less than 16%.Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71μg/mL and 252.14 ng/mL,respectively.Con⁃clusion This method has high sensitivity and good selectivity,which is suitable for the detection of carbamazepine and its metabolites in blood samples,and can be used for carbamazepine-related foren‐sic identifications.

关 键 词：法医毒物分析 液相色谱-串联质谱法 卡马西平 代谢物 10 11-二氢-10 11-环氧卡马西平 10 11-二氢-10-羟基卡马西平 

分 类 号：DF795.1[医药卫生—法医学]