Developing a Method for Quantifying Meropenem in Children-Volumetric Adsorptive Microsampling Versus Plasma Sampling.

Abstract

Meropenem is a carbapenem antibiotic often used in pediatric intensive care units due to its broad spectrum of activity. Therapeutic drug monitoring (TDM) is a useful tool to increase the effectiveness of meropenem by adjusting the dose based on plasma levels; however, the relatively large sample volume required for TDM can limit its use in children. Therefore, this study aimed to determine meropenem concentrations and consequently perform TDM effectively using the smallest possible sample volume. Volumetric absorptive microsampling (VAMS) is a sampling technology developed to collect a small, precise volume of blood. For the applicability of VAMS in TDM, plasma concentrations must be reliably calculated from whole blood (WB) collected by VAMS. VAMS technology using 10 µL of WB was evaluated and compared with EDTA-plasma sampling. High-performance liquid chromatography with UV detection was applied to quantify meropenem in VAMS and plasma samples after the removal of proteins by precipitation. Ertapenem was used as the internal standard. Samples were collected simultaneously from critically ill children receiving meropenem using VAMS and traditional sampling. It was found that no consistent factor could be determined to calculate meropenem plasma concentrations from the WB, indicating that VAMS was not reliable in the TDM of meropenem. Therefore, to reduce the required sample amount in pediatric patients, a method for quantifying meropenem from 50 µL of plasma with a lower limit of quantification of 1 mg/L was developed and successfully validated. A simple, reliable, and low-cost method was established using high-performance liquid chromatography-UV to determine the concentration of meropenem in 50 µL of plasma. VAMS using WB does not seem to be suitable for TDM of meropenem.