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 simple and robust LC–MS/MS method for the quantification of fosfomycin in human plasma and urine has been developed.
• The method uses HILIC chromatography that supports a simple treatment of fosfomycin from biological fluids.
• The developed LC–MS/MS method has been validated according to published US FDA guidelines and shows excellent performance.
• Results of a critically ill patient from a pilot pharmacokinetic study with receiving IV fosfomycin are included.
• This is the first method published that is suitable for the quantification of fosfomycin in both plasma and urine.

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.

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