ArticleEuropean journal of drug metabolism and pharmacokinetics2025
Development and Validation of an HPLC-MS/MS Method for Quantitative Bioanalysis of Lidocaine and its Metabolites in Human Plasma: Application in a Population Pharmacokinetic Study.
Article in European journal of drug metabolism and pharmacokinetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectiveLidocaine 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.
methodsAnalytes 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.
resultsThis 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.
conclusionsThis 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.
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