Development and Validation of a Strong Cation Exchange Chromatographic Column Coupled with High-Performance Liquid Chromatography Method for Meropenem and Evaluation of Its Stability in Human Plasma: Application to the Therapeutic Drug Monitoring.

Abstract

Meropenem is a wide inter-individual variability in the pharmacokinetic, and standard dosing may not be adequate in critically ill patients. Therapeutic drug monitoring is a useful tool to optimize dosing. Meropenem is the amphoteric compound with an isoelectric point of 5.15. The secondary amino group of meropenem is positively charged when pH ≤ 5.4, thus we attempted to separate by strong cation exchange (SCX) column using acetonitrile/25-mM potassium dihydrogen phosphate (pH3.0; 60:40) as mobile phase, and good peak shape and effective separation obtained. Generally, meropenem were unstable in plasma. We try to investigate stability of plasma samples using the medium QC sample with or without 3-(N-morpholino) propanesulfonic acid (MOPS) as stabilizer solutions at possible conditions during handling and storage. Meropenem showed higher stability at -80°C, and addition of MOPS might increase the short-term and extracted samples stability. This method is suitable for the quantification of meropenem in human plasma from 0.5 to 100μg/mL. The accuracy was ranged from 96.53 to 101.11% with relative standard deviation ≤ 4.76%. The method has been used for determined 63 critically ill patients treated with meropenem. During the first measurement, 11 patients showed trough levels below the target ranges despite standard dosing. Through continuous or prolonged infusion, 8/11 patients (72.73%) led to adequate trough levels. The described SCX-high-performance liquid chromatography method for meropenem in human plasma is a powerful tool for therapeutic drug monitoring.