A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Fosfomycin Concentrations in Human Prostatic Tissue

The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human prostatic tissue. The sample preparation method only required milligrams of tissue sample. Each sample was mixed with two times its weight...

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Main Authors: Matteo Conti (Author), Beatrice Giorgi (Author), Rossella Barone (Author), Milo Gatti (Author), Pier Giorgio Cojutti (Author), Federico Pea (Author)
Format: Book
Published: MDPI AG, 2024-05-01T00:00:00Z.
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001 doaj_8f8829385f9b4f63bc6fb15f56e38c52
042 |a dc 
100 1 0 |a Matteo Conti  |e author 
700 1 0 |a Beatrice Giorgi  |e author 
700 1 0 |a Rossella Barone  |e author 
700 1 0 |a Milo Gatti  |e author 
700 1 0 |a Pier Giorgio Cojutti  |e author 
700 1 0 |a Federico Pea  |e author 
245 0 0 |a A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for Measuring Fosfomycin Concentrations in Human Prostatic Tissue 
260 |b MDPI AG,   |c 2024-05-01T00:00:00Z. 
500 |a 10.3390/pharmaceutics16050681 
500 |a 1999-4923 
520 |a The aim of this study was to develop and validate a fast and sensitive bioanalytical method for the accurate quantification of fosfomycin concentrations in human prostatic tissue. The sample preparation method only required milligrams of tissue sample. Each sample was mixed with two times its weight of water and homogenized. A methanol solution that was three times the volume of the internal standard (fosfomycin-13C3) was added, followed by vortex mixing and centrifugation. After its extraction from the homogenized prostatic tissue, fosfomycin was quantified by means of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) triple quadrupole system operating in negative electrospray ionization and multiple reaction monitoring detection mode. The analytical procedure was successfully validated in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, and stability, according to EMA guidelines. The validation results, relative to three QC levels, were 9.9% for both the within-day and inter-day accuracy (BIAS%); 9.8% for within-day precision; and 9.9 for between-day precision. A marked matrix effect was observed in the measurements but was corrected by normalization with the internal standard. The average total recovery was high (approximatively 97% at the three control levels). The dynamic range of the method was 0.1-20 μg/g (R<sup>2</sup> of 0.999). Negligible carry-over was observed after the injection of highly concentrated samples. F in the sample homogenate extracts was stable at 10 °C and 4 °C for at least 24 h. In the tissue sample freeze-thaw experiments, a significant decrease in F concentrations was observed after only two cycles from −80 °C to room temperature. The novel method was successfully applied to measure fosfomycin in prostatic tissue samples collected from 105 patients undergoing prostatectomy. 
546 |a EN 
690 |a fosfomycin 
690 |a therapeutic drug monitoring 
690 |a micro samples 
690 |a prostatic tissue 
690 |a liquid chromatography-tandem mass spectrometry 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceutics, Vol 16, Iss 5, p 681 (2024) 
787 0 |n https://www.mdpi.com/1999-4923/16/5/681 
787 0 |n https://doaj.org/toc/1999-4923 
856 4 1 |u https://doaj.org/article/8f8829385f9b4f63bc6fb15f56e38c52  |z Connect to this object online.