A simple LC-MS/MS method using HILIC chromatography for the determination of fosfomycin in plasma and urine: Application to a pilot pharmacokinetic study in humans

Abstract

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, using hydrophilic interaction liquid chromatography (HILIC) chromatography for the analysis of fosfomycin in human plasma and urine, has been developed and validated. The plasma method uses a simple protein precipitation using a low volume sample (10. μL) and is suitable for the concentration range of 1 to 2000. μg/mL. The urine method involves a simple dilution of 10. μL of sample and is suitable for a concentration range of 0.1 to 10. mg/mL. The plasma and urine results, reported, respectively, are for recovery (68, 72%), inter-assay precision (≤9.1%, ≤8.1%) and accuracy (range -7.2 to 3.3%, -1.9 to 1.6%), LLOQ precision (4.7%, 3.1%) and accuracy (1.7% and 1.2%), and includes investigations into the linearity, stability and matrix effects. The method was used in a pilot pharmacokinetic study of a critically ill patient receiving IV fosfomycin, which measured a maximum and minimum plasma concentration of 222. μg/mL and 172. μg/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868. μg/mL and 591. μg/mL, respectively, after the fifth dose. The urine concentration was 2.03. mg/mL after the initial dose and 0.29. mg/mL after the fifth dose.