摘要
目的建立同时检测硬膜外麻醉致死犬血液和肝脏中利多卡因及其代谢物单乙基甘氨酰二甲苯胺(MEGX)和甘氨二甲基苯酰胺(GX)的液相色谱-离子肼质谱(LC-LIT-MS)方法。方法犬3只经硬膜外穿刺,按利多卡因硬膜外麻醉用药最大量的5倍注射(63.35 mg/kg),待呼吸、心跳等生命体征完全消失后解剖并且收集检材,样品采用液液萃取法前处理,采用离子肼质谱联用进行定性检测。高效液相色谱内标法建立工作曲线,空白添加法进行方法回收率考察。结果经硬膜外注射利多卡因后,犬出现嗜睡、流涎和抽搐等症状,犬于注射20 min后死亡。解剖见导管进入硬膜外腔隙,提示造模成功。液相色谱-离子肼质谱可以同时检测心血和肝脏中利多卡因、MEGX和GX。心血和肝脏中利多卡因的线性范围分别为0.1-100 ng/ml和0.1-100 ng/mg,最低检出限为0.004 ng,信噪比(S/N)=3;MEGX的线性范围分别为2-250 ng/ml和2-250 ng/mg,最低检出限为1 ng(S/N=3);GX的线性范围分别为2-250 ng/ml和2-250 ng/mg,最低检出限为1 ng(S/N=3)。回收率良好,方法稳定性好。结论本实验建立了同时检测生物检材中利多卡因及其代谢物的LC-LIT-MS检测方法,可用于对利多卡因及其代谢物的法医毒物动力学研究和利多卡因中毒案件的法医学鉴定。
Objective To establish a liquid chromatography ion hydrazine mass spectrometry(LC-LIT-MS)method for the simulta-neous determination of lidocaine and its metabolites monoethylglycinexylidide(MEGX)and glycinexylidide(GX)in the animal model of epidural lidocaine-induced death.Methods Three dogs were injected with 5 times the maximum dose of epidural lidocaine(63.35 mg/kg).When the vital signs such as breathing and heartbeat disappeared completely,the dogs were dissected and samples were collected.Liquid-liquid extraction method was used for the pretreatment.The qualitative analysis was performed by LC-LIT-MS.Quantitative analysis was based on an internal standard calibration curve method.Results After epidural injection of lidocaine,the dog developed symptoms such as drowsiness,salivation and convulsion,and then died 20 min after injection.Anatomically,the catheter was found to be in the epidural space.Lidocaine,MEGX and GX were all successfully detected by LC-LIT-MS.The linear range of lidocaine in blood and liver were 0.1-100 ng/ml and 0.1-100 ng/g,respectively,and the minimum detection limit was 0.004 ng(S/N=3).The linear range of MEGX was 2-250 ng/ml and 2-250 ng/mg,with a minimum detection limit of 1 ng(S/N=3).The linear range of GX was 2-250 ng/ml and 2-250 ng/mg,with a minimum detection limit of 1 ng(S/N=3).The recovery was good,and the stability of this method was good.Conclusion In this study,LC-LIT-MS is successfully established for simultaneous detection of lidocaine and its metabolites in biological samples,which could be used for forensic toxicokinetics of lidocaine and its metabolites and forensic identification of lidocaine poisoning cases.
作者
张潮
尉志文
王锦凯
牛卫芬
贠克明
ZHANG Chao;WEI Zhiwen;WANG Jinkai;NIU Weifen;YUN Keming(Department of Forensic Toxicology,School of Forensic Medicine,Shanxi Medical University,Taiyuan 030001,China)
出处
《山西医科大学学报》
CAS
2021年第8期1064-1068,共5页
Journal of Shanxi Medical University
基金
国家自然科学基金资助项目(81172906)
“十二五”国家科技支撑计划项目(2012BAK02B02)。
