Fast and Sensitive Method for Simultaneous Quantification of Meropenem and Vaborbactam in Human Plasma Microsamples by Liquid Chromatography–Tandem Mass Spectrometry for Therapeutic Drug Monitoring

Abstract

Meropenem (MRP)-Vaborbactam (VBR) is a novel beta-lactam/beta-lactamase inhibitor used for the management of difficult-to-treat Gram-negative infections. Among critically ill patients, MRP-VBR shows remarkable inter-individual variability in pharmacokinetic behavior, thus justifying the implementation of therapeutic drug monitoring (TDM) for improving real-time management in different challenging scenarios. In this study, we developed and validated a fast and sensitive Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) method for the simultaneous quantification of MRP and VBR in human plasma microsamples of 3 microliters. The analysis required only a single-step sample preparation and was performed by means of a fast chromatographic run of 4 min, followed by positive electrospray ionization and detection on a high-sensitivity triple quadrupole tandem mass spectrometer operated in multiple reaction monitoring modes. The straightforward analytical procedure was successfully validated, based on the EMA guidelines, in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, the limit of quantification, and stability. The novel method was successfully applied for simultaneously measuring MRP and VBR concentrations in more than 42 plasma samples collected from critically ill patients affected by carbapenem-resistant Gram-negative bacteria infections.

Fast and Sensitive Analysis of Fosfomycin in Human Plasma Microsamples Using Liquid Chromatography–Tandem Mass Spectrometry for Therapeutic Drug Monitoring

“…21 Thus, their use in preclinical and clinical pharmacokinetic and toxicokinetic studies has been widely investigated and implemented. [22][23][24][25][26] Microsamples of blood or plasma can be collected on specific papers, 27 polymeric tips, or capillaries. 21 They have also been recently collected using dried plasma spots.…”

Role of a Real-Time TDM-Based Expert Clinical Pharmacological Advice Program in Optimizing the Early Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Beta-Lactams among Orthotopic Liver Transplant Recipients with Documented or Suspected Gram-Negative Infections

“…For this purpose, blood samples were collected firstly at least 24 h from the starting therapy for measuring beta-lactams C ss , and then reassessed every 48-72 h whenever feasible. Total piperacillintazobactam, meropenem, ceftazidime-avibactam, and meropenem-vaborbactam plasma concentrations were determined by means of validated liquid chromatography-tandem mass spectrometry methods [17,55,56].…”