{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T03:01:59Z","timestamp":1771556519561,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u2013tandem 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\u201320 \u03bcg\/g (R2 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 \u00b0C and 4 \u00b0C for at least 24 h. In the tissue sample freeze\u2013thaw experiments, a significant decrease in F concentrations was observed after only two cycles from \u221280 \u00b0C to room temperature. The novel method was successfully applied to measure fosfomycin in prostatic tissue samples collected from 105 patients undergoing prostatectomy.<\/jats:p>","DOI":"10.3390\/pharmaceutics16050681","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T12:02:23Z","timestamp":1715947343000},"page":"681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Sensitive Liquid Chromatography\u2013Tandem Mass Spectrometry Method for Measuring Fosfomycin Concentrations in Human Prostatic Tissue"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-9674","authenticated-orcid":false,"given":"Matteo","family":"Conti","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-8706","authenticated-orcid":false,"given":"Rossella","family":"Barone","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Giorgio","family":"Cojutti","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":false,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1111\/iju.12200","article-title":"Diagnosis and Management for Urosepsis","volume":"20","author":"Wagenlehner","year":"2013","journal-title":"Int. J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1128\/AAC.01519-08","article-title":"Oral and Parenteral Therapeutic Options for Outpatient Urinary Infections Caused by Enterobacteriaceae Producing CTX-M Extended-Spectrum \u03b2-Lactamases","volume":"53","author":"Prakash","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-Resistant, Extensively Drug-Resistant and Pandrug-Resistant Bacteria: An International Expert Proposal for Interim Standard Definitions for Acquired Resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.12968\/hmed.2006.67.2.20472","article-title":"Multi-Resistant Escherichia coli Sepsis Following Transrectal Ultrasound-Guided Prostate Biopsy","volume":"67","author":"Davidson","year":"2006","journal-title":"Br. J. Hosp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/jgid.jgid_72_17","article-title":"Nitrofurantoin and Fosfomycin for Extended Spectrum Beta-Lactamases Producing Escherichia coli and Klebsiella pneumoniae","volume":"10","author":"Tulara","year":"2018","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3390\/idr14040067","article-title":"Oral Fosfomycin Formulation in Bacterial Prostatitis: New Role for an Old Molecule-Brief Literature Review and Clinical Considerations","volume":"14","author":"Marino","year":"2022","journal-title":"Infect. Dis. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e02560-17","DOI":"10.1128\/AAC.02560-17","article-title":"Pharmacokinetics and Pharmacodynamics of Fosfomycin and Its Activity against Extended-Spectrum-\u03b2-Lactamase-, Plasmid-Mediated AmpC-, and Carbapenemase-Producing Escherichia coli in a Murine Urinary Tract Infection Model","volume":"62","author":"Zykov","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00345-016-1867-6","article-title":"Antimicrobial Prophylaxis for Transrectal Ultrasound-Guided Prostate Biopsy: Fosfomycin Trometamol, an Attractive Alternative","volume":"35","author":"Cai","year":"2017","journal-title":"World J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"863","DOI":"10.5489\/cuaj.3068","article-title":"The Use of Prophylactic Single-Dose Fosfomycin in Patients Who Undergo Transrectal Ultrasound-Guided Prostate Biopsy: A Prospective, Randomized, and Controlled Clinical Study","volume":"9","author":"Sen","year":"2015","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bouiller, K., Zayet, S., Lalloz, P.-E., Potron, A., Gendrin, V., Chirouze, C., and Klopfenstein, T. (2022). Efficacy and Safety of Oral Fosfomycin-Trometamol in Male Urinary Tract Infections with Multidrug-Resistant Enterobacterales. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020198"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13021","DOI":"10.1111\/and.13021","article-title":"Pharmacodynamic and Pharmacokinetic Studies and Prostatic Tissue Distribution of Fosfomycin Tromethamine in Bacterial Prostatitis or Normal Rats","volume":"50","author":"Fan","year":"2018","journal-title":"Andrologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/cid\/civ436","article-title":"Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs: Figure 1","volume":"61","author":"Grayson","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.30526\/35.3.2826","article-title":"Subject Review on Some Analytical Methods for Determination of Fosfomycin Drugs","volume":"35","author":"Khalil","year":"2022","journal-title":"Ibn AL-Haitham J. Pure Appl. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sobels, A., Lentjes, K.J., Froeling, F.M.J.A., Van Nieuwkoop, C., and Wilms, E.B. (2022). Serum and Prostatic Tissue Concentrations of Cefazolin, Ciprofloxacin and Fosfomycin after Prophylactic Use for Transurethral Resection of the Prostate. Antibiotics, 12.","DOI":"10.3390\/antibiotics12010022"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/jac\/dkv067","article-title":"Optimal Timing of Oral Fosfomycin Administration for Pre-Prostate Biopsy Prophylaxis","volume":"70","author":"Rhodes","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/FTD.0000000000001158","article-title":"Fast and Sensitive Analysis of Fosfomycin in Human Plasma Microsamples Using Liquid Chromatography\u2013Tandem Mass Spectrometry for Therapeutic Drug Monitoring","volume":"46","author":"Barone","year":"2023","journal-title":"Ther. Drug Monit."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhanel, G.G., Zhanel, M.A., and Karlowsky, J.A. (2018). Oral Fosfomycin for the Treatment of Acute and Chronic Bacterial Prostatitis Caused by Multidrug-Resistant Escherichia coli. Can. J. Infect. Dis. Med. Microbiol., 2018.","DOI":"10.1155\/2018\/1404813"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1093\/cid\/cit704","article-title":"Is Fosfomycin a Potential Treatment Alternative for Multidrug-Resistant Gram-Negative Prostatitis?","volume":"58","author":"Gardiner","year":"2014","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jchromb.2017.07.036","article-title":"A Fast and Sensitive LC\u2013MS\/MS Method for the Quantification of Fosfomycin in Human Urine and Plasma Using One Sample Preparation Method and HILIC Chromatography","volume":"1061\u20131062","author":"Wijma","year":"2017","journal-title":"J. Chromatogr. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1515\/cclm-2020-1196","article-title":"A Validated LC-MS\/MS Method for the Simultaneous Quantification of the Novel Combination Antibiotic, Ceftolozane\u2013Tazobactam, in Plasma (Total and Unbound), CSF, Urine and Renal Replacement Therapy Effluent: Application to Pilot Pharmacokinetic Studies","volume":"59","author":"Parker","year":"2021","journal-title":"Clin. Chem. Lab. Med. CCLM"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Goh, K.K.-K., Toh, W.G.-H., Hee, D.K.-H., Ting, E.Z.-W., Chua, N.G.S., Zulkifli, F.I.B., Sin, L.-J., Tan, T.-T., Kwa, A.L.-H., and Lim, T.-P. (2022). Quantification of Fosfomycin in Combination with Nine Antibiotics in Human Plasma and Cation-Adjusted Mueller-Hinton II Broth via LCMS. Antibiotics, 11.","DOI":"10.3390\/antibiotics11010054"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Magr\u00e9ault, S., Jaureguy, F., Zahar, J.-R., M\u00e9cha\u00ef, F., Toinon, D., Cohen, Y., Carbonnelle, E., and Jullien, V. (2022). Automated HPLC-MS\/MS Assay for the Simultaneous Determination of Ten Plasma Antibiotic Concentrations. J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 1211.","DOI":"10.1016\/j.jchromb.2022.123496"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mula, J., Chiara, F., Manca, A., Palermiti, A., Maiese, D., Cusato, J., Simiele, M., De Rosa, F.G., Di Perri, G., and De Nicol\u00f2, A. (2023). Analytical Validation of a Novel UHPLC-MS\/MS Method for 19 Antibiotics Quantification in Plasma: Implementation in a LC-MS\/MS Kit. Biomed. Pharmacother., 163.","DOI":"10.1016\/j.biopha.2023.114790"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gandhi, A., Matta, M., Garimella, N., Zere, T., and Weaver, J. (2018). Development and Validation of a LC-MS\/MS Method for Quantitation of Fosfomycin\u2014Application to in Vitro Antimicrobial Resistance Study Using Hollow-Fiber Infection Model. Biomed. Chromatogr., 32.","DOI":"10.1002\/bmc.4214"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/1120009X.2021.1963617","article-title":"Fosfomycin Therapeutic Drug Monitoring in Real-Life: Development and Validation of a LC-MS\/MS Method on Plasma Samples","volume":"34","author":"Baldelli","year":"2022","journal-title":"J. Chemother."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/5\/681\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:44:20Z","timestamp":1760107460000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/5\/681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["pharmaceutics16050681"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16050681","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,17]]}}}