title: 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 i.v. 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 591μg/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.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. Electronic address: suzanne.parker@uq.edu.au.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Parker
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016638:Critical Illness; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D005578:Fosfomycin / Q000097:blood / Q000652:urine; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D057230:Limit of Detection; D015394:Molecular Structure; D010865:Pilot Projects; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: Antibiotic; Fosfomycin; HILIC; LC–MS/MS; Pharmacokinetic