Foong Keng Wah, Mohamad Haron Didi Erwandi, Chaw Sook Hui, Lo Yoke Lin, Omer Noridayu, Loh Pui San
Department of Anaesthesiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Shimadzu Universiti Malaya HIR Testing and Research Analytical Laboratory (SUTRAlab), Department of Research Development, Deputy Vice-Chancellor (Research and Innovation), University of Malaya, 50603, Kuala Lumpur, Malaysia.
Eur J Drug Metab Pharmacokinet. 2025 Sep 12. doi: 10.1007/s13318-025-00964-1.
Lidocaine is increasingly used perioperatively as a systemic analgesic. Quantification of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), is essential for understanding its pharmacokinetics and pharmacodynamics. Existing methods have limitations in throughput, concentration ranges, or do not simultaneously measure lidocaine and metabolites. This study aims to develop and validate a simple, rapid, and robust high-performance liquid chromatography-mass spectrometry (HPLC-MS)/MS method for their simultaneous quantification in plasma from surgical patients receiving intravenous lidocaine.
Analytes were extracted from 75 µL of plasma by protein precipitation with 300 µL of methanol containing lidocaine-d10 (internal standard). After centrifugation for 5 minutes and filtration, 5 µL was injected onto a Phenomenex Luna C8(2) column (100 × 2.0 mm, 5 µm), achieving chromatographic separation within 5 minutes by gradient elution with 0.01% formic acid in water (mobile phase A) and acetonitrile-methanol 50:50 (mobile phase B). Mass spectrometry detection employed positive electrospray ionization with multiple reaction monitoring. The method uses a widely accessible HPLC-MS/MS platform, requires low plasma volume, and features streamlined sample preparation.
This method demonstrated good selectivity and specificity, minimal carryover, and reproducible recovery and matrix effects. Calibration curves were linear over 0.01-5 mg/L for lidocaine and 0.01-1.5 mg/L for MEGX and GX. Within-day and between-day accuracy and precision met acceptance criteria, and analytes remained stable under relevant conditions.
This validated assay requires low plasma volume and minimal preparation for simultaneous quantification of lidocaine and metabolites. It was successfully applied in a population pharmacokinetic study of surgical patients receiving intravenous lidocaine, supporting optimized dosing strategies.
利多卡因在围手术期越来越多地用作全身镇痛药。定量分析利多卡因及其活性代谢产物单乙基甘氨酰二甲苯胺（MEGX）和甘氨酰二甲苯胺（GX）对于理解其药代动力学和药效学至关重要。现有方法在通量、浓度范围方面存在局限性，或者不能同时测定利多卡因及其代谢产物。本研究旨在开发并验证一种简单、快速且稳健的高效液相色谱 - 质谱联用（HPLC - MS）/ MS方法，用于同时定量接受静脉注射利多卡因的手术患者血浆中的这些物质。
通过用含利多卡因 - d10（内标）的300 μL甲醇进行蛋白沉淀，从75 μL血浆中提取分析物。离心5分钟并过滤后，注入5 μL到Phenomenex Luna C8(2)柱（100×2.0 mm，5 µm）上，通过用0.01%甲酸水溶液（流动相A）和乙腈 - 甲醇50:50（流动相B）进行梯度洗脱，在5分钟内实现色谱分离。质谱检测采用正电喷雾电离和多反应监测。该方法使用广泛可用的HPLC - MS/MS平台，所需血浆量少，且样品制备流程简化。
该方法显示出良好的选择性和特异性、最小的残留、可重复的回收率和基质效应。利多卡因的校准曲线在0.01 - 5 mg/L范围内呈线性，MEGX和GX的校准曲线在0.01 - 1.5 mg/L范围内呈线性。日内和日间的准确度和精密度符合验收标准，并且分析物在相关条件下保持稳定。
这种经过验证的检测方法所需血浆量少且样品制备简单，可同时定量利多卡因及其代谢产物。它已成功应用于接受静脉注射利多卡因的手术患者群体药代动力学研究，支持优化给药策略。
