Development and validation of a UHPLC diode array detector method for meropenem quantification in human plasma

Objectives: Meropenem is a β-lactam antibiotic frequently used to treat serious infections in intensive care unit patients. The main objective was to develop and validate a sensitive and specific ultra high performance liquid chromatography method with photodiode array detection for the quantitation of meropenem in human plasma. The applicability of the method for meropenem monitoring was also examined.

Design and methods: The validation of the method was performed following the FDA's guidelines for bioanalytical methods. In parallel, the method was applied for monitoring meropenem in forty plasma samples from ten critically ill patients treated intravenously at a total dose of 1 g. Drug levels were measured in each patient at 0 h, 2 h, 4 h and 8 h after meropenem infusion.

Results: With this method, intraday and day-to-day variation was below 10%; intraday and day-to-day accuracy was between 94% and 114%; the limit of quantification was 0.5 μg/mL and recovery was above 70%. The method was successfully applied to quantitate meropenem concentrations and the results showed significant pharmacokinetic interindividual variability. Of special interest is that 50% of treated patients had meropenem plasma levels below the minimum inhibitory concentration at 8h after the start of infusion, which was strongly related to creatinine clearance >60 mL/min.

Conclusions: The method meets the requirements to be applied for meropenem concentration measurements in pharmacokinetics studies and clinical routine. The results suggest the need for therapeutic drug monitoring of meropenem in treated critically-ill patients.