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

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 mu L) and is suitable for the concentration range of 1 to 2000 mu g/mL. The urine method involves a simple dilution of 10 mu L 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 mu g/mL and 172 mu g/mL, respectively, after the initial dose, and a maximum and minimum plasma concentration of 868 mu g/mL and 591 mu g/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. (C) 2014 Elsevier B.V. All rights reserved.