LC-MS/MS法检测人血液中的利多卡因及其代谢物

Determination of lidocaine and its metabolites in human blood by LC-MS/MS

目的建立人血液样品中利多卡因及其代谢物单乙基甘氨酰二甲苯胺(MEGX)和甘氨酰二甲苯胺(GX)的液相色谱-串联质谱(LC-MS/MS)分析方法。方法人血液样品经乙腈沉淀蛋白后,Zorbax RRHD Plus C18柱(2.1mm×50mm,1.8μm)分离,以0.1%甲酸和乙腈为流动相进行洗脱。质谱采用电喷雾正离子化(ESI+),多反应监测扫描模式。结果血液中利多卡因、MEGX和GX在相应范围内线性良好,相关系数(r>0.9950)。在血液中检出限分别为0.1 ng/mL、0.5 ng/mL和0.2 ng/mL,方法回收率为92.7%~103.9%,准确度为92.9%~113.1%,日内、日间精密度的相对标准偏差均不超过13.0%。在1例肌肉注射利多卡因死者心血中利多卡因、MEGX和GX的质量浓度分别为1.520μg/mL、0.019μg/mL和0.266μg/mL。结论本方法灵敏度高、选择性好,适用于血液中利多卡因及其代谢物的检测,可为利多卡因临床治疗过程中的药物浓度监测和法医学鉴定提供技术支撑。

Objective To establish a LC-MS/MS method for determination of lidocaine and its metabolites monoethylglycinexylidide(MEGX)and glycinexylidide(GX)in human blood.Methods Acetonitrile was added to blood samples for precipitating protein.Chromatographic seperation was performed on a Zorbax RRHD Plus C18 column(2.1 mm×50 mm,1.8μm),and the mobile phase was consisted of 0.1%formic acid and acetonitrile.Qualitative and quantitative analysis was performed in the multiple reaction monitoring mode coupled with an electrospray ionization source under positive ion mode(ESI+).Results The linearity of lidocaine,MEGX and GX in blood was good within corresponding linear limitation,with correlation coefficients(r>0.9950).The limits of detection were 0.1 ng/mL,0.5 ng/mL,and 0.2 ng/mL,respectively.The recovery and accuracy of the lidocaine,MEGX and GX ranged from 92.7%to 103.9%,and 92.9%to 113.1%,respectively.The relative standard deviations of the intra-day and inter-day precisions were no more than 13.0%.In a case of death after intramuscular injection of lidocaine,the mass concentrations of blood lidocaine,MEGX and GX in the deceased were 1.520μg/mL,0.019μg/mL and 0.266μg/mLrespectively.Conclusion This method is sensitive and accurate for the detection of lidocaine and its metabolites in human blood,which can be used to analyse blood samples following a intramuscular administration of lidocaine.