A rapid liquid chromatography-tandem mass spectrometry for the quantification of Fosfomycin in plasma, urine, and aqueous fluids

A simple and fast ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the analysis of Fosfomycin in different matrices (human plasma/urine, and aqueous fluid) has been established and validated. Sample cleanup consists, depending on the matrix used, on protein precipitation or dilution with methanol containing isotopically labeled Fosfomycin as internal standard. Compounds, separated on a Luna Omega PS C-18 column, were detected in multiple reactions monitoring in negative ion mode using API4000 system. With a total run time of 2 min and using low volume of samples (plasma: 10 mu l, urine: 2 mu l, and aqueous fluid: 5 mu l), the covered ranges were: plasma (12.5-800 mu g/mL), urine (62.5-4000 mu g/mL), and aqueous fluid (1-160 mu g/mL). The method proved to be precise and accurate. The inaccuracy and imprecision in each matrix at the four tested quality controls including the lower limit of quantification were:: plasma (<= 6.5%, <= 8%), urine (<= 5.8%, <= 6.3%), and aqueous fluid (<= 10.6%, <= 12%). The method is fast and robust which makes it relevant for pharmacolcinetic studies and therapeutic drug monitoring. The appropriateness of the developed method in clinical application is also confirmed.