title: A validated method for the quantification of fosfomycin on dried plasma spots by HPLC-MS/MS: application to a pilot pharmacokinetic study in humans.
abstract: Quantification of fosfomycin in the plasma samples of patients is the basis of clinical pharmacokinetic studies from which evidence based dosing regimens can be devised to maximise antibiotic effectiveness against a pathogen. We have developed and validated a LC-MS/MS method to quantify fosfomycin using dried plasma spot sampling. Following HILIC chromatography, fosfomycin and ethylphosphonic acid, used as internal standard, were measured using negative-ion multiple reaction monitoring. The method was linear over the calibration range of 5-2000mg/L of fosfomycin. Intra-day assay results for dried plasma spot quality control samples at 15.6, 79.9 and 1581mg/L of fosfomycin had precision of ±4.2, 8.2, and 2.0%, respectively, and accuracy of +3.9, -0.1, and -1.2%, respectively. Recovery of fosfomycin from dried plasma spots was calculated as 83.6% and the dried plasma spot samples were found to be stable stored at room temperature for three months and when stored for four hours at 50°C. A Bland-Altman plot comparing DPS to plasma sampling found a negative bias of 16.6%, with all but one sample within the mean limits of agreement (-2.6 to 30.6%). Dried plasma spot sampling provides a useful tool for pharmacokinetic research of fosfomycin.
authors: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia. Electronic address: suzanne.parker@uq.edu.au.
authors: Suzanne L
authors: SL
authors: Parker
authors: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane Hospital, Brisbane, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia.
authors: Jeffrey
authors: J
authors: Lipman
authors: Medical School, University of Athens, Athens, Greece; Internal Medicine Department, Hygeia Hospital, Athens, Greece.
authors: George
authors: G
authors: Dimopoulos
authors: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Department of Pharmacy, Royal Brisbane Hospital, Brisbane, Australia.
authors: Jason A
authors: JA
authors: Roberts
authors: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors: Steven C
authors: SC
authors: Wallis
mesh_terms: D061605:Administration, Intravenous; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D059788:Dried Blood Spot Testing / Q000379:methods* / Q000592:standards; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D004355:Drug Stability; D005578:Fosfomycin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D010865:Pilot Projects; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000592:standards; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin
keywords: Antibiotic; Dried plasma spots; Fosfomycin; LC–MS/MS; Pharmacokinetic