Rapid and Sensitive Liquid Chromatography–Tandem Mass Spectrometry Method for Determination of Monoethylglycinexylidide

Abstract

A large body of evidence currently documents the utility of the MEGX test for real-time assessment of liver function in transplantation, critical care medicine, and various experimental models (1). The test is based on the conversion of lidocaine to its deethylated metabolite monoethylglycinexylidide (MEGX), primarily through the hepatic cytochrome P450 system. In the standard MEGX test, an intravenous bolus of a small lidocaine dose (1 mg/kg) is administered over 2 min. Blood specimens are collected for serum MEGX determination both before and at 15 and/or 30 min after lidocaine administration. The most commonly used method to measure serum MEGX has been an automated fluorescence polarization immunoassay (Abbott Laboratories) with a detection limit of 3 μg/L. This test, however, is no longer commercially available. HPLC methods with ultraviolet detection (2)(3) and gas chromatographic (GC) procedures with ionization or nitrogen-phosphorous detection (4)(5) were originally reported, but all of these techniques had a limit of quantification >10 μg/L. Several studies have shown that transplant candidates with MEGX test results <10 μg/L have a particularly poor 1-year survival rate (6)(7)(8). An improved HPLC method with fluorescence detection (9) and a capillary GC method with nitrogen-phosphorus detection (10) were therefore developed that achieved an adequate analytical sensitivity with limits of detection of ∼1–2 μg/L. The disadvantage of the HPLC method with fluorescence detection is the necessity to derivatize MEGX. Because of its flexibility and high specificity, liquid chromatography–tandem mass spectrometry (LC-MS-MS) is finding increasing application for the quantification of numerous analytes. We now describe a reliable, simple, sensitive, and rapid procedure for determining MEGX in serum by LC-MS-MS. This procedure also allows the simultaneous measurement of serum lidocaine concentrations in the same sample. MEGX hydrochloride and lidocaine hydrochloride were kind gifts from Astra (Stockholm, Sweden). The internal …