HPLC-MS/MS测定人体血浆中利多卡因及其代谢物浓度

Determination of Lidocaine and Its Metabolites in Human Plasma by Liquid Chromatography in Combination with Tandem Mass Spectrometry

目的建立高效液相-串联质谱法(HPLC-MS/MS)测定人体血浆中利多卡因(lidocaine,LDC)及其代谢物单乙基甘氨二甲基苯酰胺(MEGX)和甘氨二甲基苯酰胺(GX)的浓度。方法采用API3000型HPLC-MS/MS液质联用系统,Ultimate C18分析柱(50×4.6 mm,5μm),甲氧苄啶作为内标,流动相为甲醇∶5 mmol/L醋酸铵=50∶50(甲酸调pH5.0),流速0.2 mL/min。样品在碱性条件下用乙酸乙酯提取浓集后进样,选择性离子监测模式检测。结果 LDC的线性范围为15.625~2000 ng/mL,MEGX和GX的线性范围均为1.5625~200 ng/mL。LDC、MEGX和GX的最低定量限分别为:15.625、1.5625和1.5625 ng/mL。结论该方法具有快速简便、灵敏准确等特点,可满足利多卡因及其代谢物临床药物浓度测定的需要。

Objective To establish a liquid chromatography tandem mass spectrometry(HPLC-MS/MS) method for the determination of lidocaine(LDC) and its metabolites,monoethylglycinexylidide(MEGX) and glycinexylidide(GX),in human plasma.Methods The assay was conducted with an API 3000 HPLC-MS/MS system consisted of a Ultimate C18 column(50×4.6 mm,5 μm). The mobile phase consisted of methanol: 5 mmol/L ammonium acetate(50:50,pH was adjusted to 5.0 by formic acid) and the flow rate was set at 0.2 mL/min.The alkalinized sample was extracted with ethyl acetate.After evaporation of the organic layer,the residue was dissolved in mobile phase and the drug was determined by HPLC-MS/MS using electrospray ionization.Results The calibration curve was linear in a range from 15.625 to 2000 ng/mL for LDC.Linear calibration curves were obtained in the range of 1.5625 to 200 ng/mL for both for MEGX and GX.The limit of quantification for LDC,MEGX and GX was set at 15.625,1.5625 and 1.5625 ng/mL.Conclusion This method for the quantitative determination of lidocaine and its metabolites in human plasma is simple,rapid,sensitive and accurate.Therefore it can be used for the determination of lidocaine and its metabolites in clinical practice.