Simultaneous Retrodialysis by Drug for Cefuroxime Using Meropenem as an Internal Standard—A Microdialysis Validation Study

Abstract

Microdialysis is a valuable pharmacokinetic tool for obtaining samples of drug concentrations from tissues of interest. When an absolute tissue concentration is needed, a calibration of the microdialysis catheter is required. The use of an internal standard offers a number of advantages compared to standard calibration methods. However, meticulous validation both in vitro and in vivo is needed, as this method requires an internal standard with physiochemical similarities to the analyte of interest with no interference. A series of in vitro and in vivo setups were conducted to determine the relative recovery by gain and by loss for cefuroxime, with and without a constant meropenem concentration. The cefuroxime and meropenem concentrations were determined using ultra-HPLC. The main finding was that cefuroxime and meropenem relative recovery behaved similarly both in vitro and in vivo, signifying that meropenem is a representative internal standard for cefuroxime. Furthermore, cefuroxime relative recovery in vitro was not affected by either the cefuroxime concentration or the presence of meropenem, and the in vivo meropenem relative recovery was constant over 6 h.