Development and Validation of a Rapid LC–MS/MS Method for the Quantification of Contezolid in Human Plasma and Liver, and Its Application to a Pharmacokinetic Study in Liver Transplant Patients

A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantification of contezolid in human plasma and liver tissue. Sample preparation was performed by protein precipitation using linezolid as the internal standard. Chromatographic separation was achieved on an ACQUITY BEH C18 column (2.1 × 50 mm, 1.8 μm) with a mobile phase consisting of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B), delivered at a flow rate of 0.5 mL/min. Quantification was performed in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 409.1 → 269.1 for contezolid and m/z 338.1 → 296.2 for linezolid. The method showed excellent linearity over the ranges of 20-10,000 ng/mL in plasma and 100-50,000 ng/g in liver tissue. Full validation confirmed that the method met regulatory standards for accuracy, precision, sensitivity, selectivity, stability, matrix effects, carryover, and interference. The validated assay was successfully applied to a pharmacokinetic study of contezolid in liver transplant recipients. In conclusion, this robust, efficient, and cost-effective LC-MS/MS method provides a valuable tool for the determination of contezolid in clinical and pharmacokinetic research.