ESTABLISHMENT OF A METHOD FOR MONITORING MEROPENEM CONCENTRATIONS IN PATIENTS WITH SEVERE ACUTE PANCREATITIS

Objective: To establish a population pharmacokinetic (PPK) model for meropenem in patients with severe acute pancreatitis (SAP), providing a valuable basis and method for developing individualized meropenem dosing regimens tailored to the pathophysiological state of SAP patients; Methods: Meropenem concentrations in plasma and abdominal drainage fluid were monitored using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and homogeneous enzyme immunoassay. Nonlinear mixed-effects modeling was performed using Phoenix software; Results: (1) Meropenem concentration determination: A total of 20 SAP patients were enrolled, providing 99 qualified plasma samples and 42 qualified abdominal drainage fluid samples. Meropenem and the internal standard (metformin) were well separated in both plasma and drainage fluid samples, demonstrating good specificity. Meropenem showed excellent linearity within the ranges of 0.5 - 200 μg/mL in plasma and 0.1 - 10 μg/mL in drainage fluid. All methodological validation results fell within acceptable limits, with RSD ≤ 15%; Conclusion: This study established an LC-MS/MS method (referenced and quality-controlled by homogeneous enzyme immunoassay) for determining meropenem concentrations. The validated method is suitable for clinical therapeutic drug monitoring (TDM) of meropenem, particularly in critically ill ICU patients.