Quantitative Determination of Fosfomycin in 10 μL of Plasma and Dialysate by Hydrophilic Interaction Liquid Chromatography Electrospray Ionization Mass Spectrometry

Abstract

Fosfomycin is an antibiotic with a broad spectrum of activity against many multidrug-resistant bacterial strains. It is mainly excreted unchanged by the kidneys, and its half-life therefore depends on kidney function which varies considerably among individuals, and within individuals over time. Proper fosfomycin dosing thus depends on assaying blood concentration of the drug. We developed and validated a simple, sensitive and specific chromatography assay, which was coupled to electrospray ionization mass spectrometry for determination of fosfomycin. Separation of fosfomycin was based on the method of the hydrophilic interaction liquid chromatography; specifically, plasma and dialysate samples were acidified and the protein precipitated with acetonitrile. The calibration curves showed excellent coefficients of determination (R2 > 0.999) over the relevant concentration range of 25–700 μg/mL. Intraday precision was 1.1–1.2% and accuracy was −5.9% to 0.9% for quality control samples. Interday precision was 2.9–3.4% and accuracy was −3.7% to 5.5%. Extraction recovery was ≥87% and matrix effects ranged from 2.2% to 4.3%. After laboratory validation, the method was successfully applied to clinical samples.

Quantification of Fosfomycin in Combination with Nine Antibiotics in Human Plasma and Cation-Adjusted Mueller-Hinton II Broth via LCMS

“…Over the past five years, mass spectrometry-based methods to measure fosfomycin in various matrices such as plasma [ 9 , 10 , 11 ], plasma dried spots [ 12 ], growth media [ 13 ], and urine [ 11 , 14 , 15 ] have been reported to support PK/PD optimization of fosfomycin therapy. Interestingly, these methods solely measure fosfomycin.…”

Stability Study of Fosfomycin in Elastomeric Pumps at 4 °C and 34 °C: Technical Bases for a Continuous Infusion Use for Outpatient Parenteral Antibiotic Therapy

“…Optimization of the mass conditions has been performed via the infusion of reference standards of FOS and corresponding IS at the concentration of 1 ppm in water/methanol 50% v / v at 5.0 μL/min into the mass spectrometer, in combination with the flow from the chromatographic system at medium concentrations phases (Phase A and Phase B 50% v / v ). FOS exhibited two transitions: 137.0 > 78.9 m / z and 137.0 > 62.8; the first was used to quantify (quantification trace), whereas the second was used to confirm peak identity (secondary ion trace), in accordance with previously reported methods [ 27 , 29 , 30 , 31 , 36 , 37 , 38 ]. Dwell Time was 25 ms, Entrance Voltage was −12 V and Collision Energy was 20 and 40 eV for the First Ion Trace and for the Second Ion Trace, respectively.…”

“…Recent data suggest high thermal stability of FOS powders and solutions as well long stability, even at room temperature, in biological samples using different approaches ranging from Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC) to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) or microbiological testing [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

ICP-MS: a tool for detection and quantitation of fosfomycin residues in cleaning samples of finished product by estimation of phosphorous load

“…19 In mass spectrometry, atmospheric ionization models are widely used in cleaning assessment methods. In this manner, HPLC-MS/MS [20][21][22][23] (LOQ = 0.75 mg L −1 ) and GC could be useful to analyse fosfomycin with specic derivatization. 24 Nevertheless, the distinctiveness of the structural and physicochemical parameters of fosfomycin directed us to use the ICP-MS technique as a superior choice for cleaning method development.…”

“…19 In mass spectrometry, atmospheric ionization models are widely used in cleaning assessment methods. In this manner, HPLC-MS/MS 20–23 (LOQ = 0.75 mg L −1 ) and GC could be useful to analyse fosfomycin with specific derivatization. 24…”