Simultaneous determination of lidocaine and its active metabolites in plasma by UPLC–MS/MS and application to a clinical pharmacokinetic study in liver cancer patients with laparoscopic hepatectomy

Abstract

Lidocaine, widely used as a local anesthetic, has anti-inflammatory and inhibitory effects on tumor recurrence and metastasis. To investigate the pharmacokinetics of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy, a fast and sensitive analytical technique was developed. The method was adequately validated with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) to simultaneously determine the concentration of lidocaine and its metabolites in plasma. The chromatographic separation was achieved on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) by gradient elution with a mobile phase of A (formic acid–water (1:1000, v/v)) and B (formic acid-acetonitrile (1:1000, v/v)). The accuracy and precision were verified within the concentration ranges of 10–5000 ng/mL for lidocaine, 2–1000 ng/mL for monoethylglycinexylidide (MEGX) and 2–500 ng/mL for glycinexylidide (GX). The selectivity, carry-over effect, interference between the analytes and internal standard (IS), precision and accuracy, matrix effect extraction recovery, dilution integrity and stability were satisfactory for the relevant guideline standards. The method was successfully applied to the pharmacokinetic study of lidocaine in liver cancer patients undergoing laparoscopic hepatectomy. After receiving a bolus and continuous infusion, the mean peak concentration of lidocaine was 2097 ng/mL for lidocaine, 336.6 ng/mL for MEGX and 72.66 ng/mL for GX, respectively. The mean peak time was 2.89 h for lidocaine, 5.14 h for MEGX and 9.88 h for GX, respectively. In addition, the mean half-life was 4.19 h for lidocaine and 6.92 h for MEGX. In this study, we found that the metabolism of lidocaine and MEGX might be affected by the hepatic blood flow occlusion or liver injury.