Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma
Abstract Background Malaria still poses a significant burden on global health, with millions of cases reported annually and rising resistance to current treatments, emphasizing the need for new therapeutic strategies. Fosmidomycin, initially recognized for its antibacterial properties, has emerged a...
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BMC
2025-07-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-025-05489-1 |
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| author | Christoph Pfaffendorf Keanu D. Sackmann Johannes Mischlinger Jean Claude Dejon-Agobé Oumou Maïga-Ascofaré Ebenezer Ahenkan Ayôla Akim Adegnika Michael Ramharter Philipp Uhl Gert Fricker Sebastian G. Wicha |
| author_facet | Christoph Pfaffendorf Keanu D. Sackmann Johannes Mischlinger Jean Claude Dejon-Agobé Oumou Maïga-Ascofaré Ebenezer Ahenkan Ayôla Akim Adegnika Michael Ramharter Philipp Uhl Gert Fricker Sebastian G. Wicha |
| author_sort | Christoph Pfaffendorf |
| collection | DOAJ |
| description | Abstract Background Malaria still poses a significant burden on global health, with millions of cases reported annually and rising resistance to current treatments, emphasizing the need for new therapeutic strategies. Fosmidomycin, initially recognized for its antibacterial properties, has emerged as a promising candidate in the fight against malaria. Methods In this study, a sensitive and robust LC–MS/MS method for quantifying fosmidomycin in human and rat plasma was developed and validated. Plasma samples were prepared using a simple protein precipitation method with 10% trichloroacetic acid (TCA). The assay featured a rapid run time of 5 min, and validation was performed according to the European Medicines Agency's guidelines. Results The method validation confirmed its selectivity, linearity, accuracy, precision, and stability. Notably, the calibration range was established from 0.25 to 15 mg/L, demonstrating improvements over previous methodologies with lower limits of quantification of 0.5–1.0 mg/L. Using the developed LC–MS/MS method, plasma samples were analysed from a clinical trial conducted in Gabon, as well as from a pharmacokinetic study involving male Wistar rats, revealing viable pharmacokinetic profiles for fosmidomycin. Conclusions These findings confirm the utility of the developed analytical method for supporting the clinical development of fosmidomycin as a potential therapy for malaria. |
| format | Article |
| id | doaj-art-0c9fc3f11fb649db9cbbc67ceab0651d |
| institution | Kabale University |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj-art-0c9fc3f11fb649db9cbbc67ceab0651d2025-08-20T03:42:34ZengBMCMalaria Journal1475-28752025-07-0124111110.1186/s12936-025-05489-1Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasmaChristoph Pfaffendorf0Keanu D. Sackmann1Johannes Mischlinger2Jean Claude Dejon-Agobé3Oumou Maïga-Ascofaré4Ebenezer Ahenkan5Ayôla Akim Adegnika6Michael Ramharter7Philipp Uhl8Gert Fricker9Sebastian G. Wicha10Institute of Pharmacy, Dept. of Clinical Pharmacy, University of HamburgInstitute of Pharmacy, Dept. of Clinical Pharmacy, University of HamburgCentre for Tropical Medicine, Department of Medicine, Bernhard Nocht Institute for Tropical Medicine, University Medical Center Hamburg-EppendorfCentre de Recherches Médicales de LambarénéKumasi Centre for Collaborative Research in Tropical MedicineKumasi Centre for Collaborative Research in Tropical MedicineCentre de Recherches Médicales de LambarénéCentre for Tropical Medicine, Department of Medicine, Bernhard Nocht Institute for Tropical Medicine, University Medical Center Hamburg-EppendorfInstitute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-UniversityInstitute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls-UniversityInstitute of Pharmacy, Dept. of Clinical Pharmacy, University of HamburgAbstract Background Malaria still poses a significant burden on global health, with millions of cases reported annually and rising resistance to current treatments, emphasizing the need for new therapeutic strategies. Fosmidomycin, initially recognized for its antibacterial properties, has emerged as a promising candidate in the fight against malaria. Methods In this study, a sensitive and robust LC–MS/MS method for quantifying fosmidomycin in human and rat plasma was developed and validated. Plasma samples were prepared using a simple protein precipitation method with 10% trichloroacetic acid (TCA). The assay featured a rapid run time of 5 min, and validation was performed according to the European Medicines Agency's guidelines. Results The method validation confirmed its selectivity, linearity, accuracy, precision, and stability. Notably, the calibration range was established from 0.25 to 15 mg/L, demonstrating improvements over previous methodologies with lower limits of quantification of 0.5–1.0 mg/L. Using the developed LC–MS/MS method, plasma samples were analysed from a clinical trial conducted in Gabon, as well as from a pharmacokinetic study involving male Wistar rats, revealing viable pharmacokinetic profiles for fosmidomycin. Conclusions These findings confirm the utility of the developed analytical method for supporting the clinical development of fosmidomycin as a potential therapy for malaria.https://doi.org/10.1186/s12936-025-05489-1FosmidomycinLC–MS/MSPharmacokineticsBioanalysisMalaria |
| spellingShingle | Christoph Pfaffendorf Keanu D. Sackmann Johannes Mischlinger Jean Claude Dejon-Agobé Oumou Maïga-Ascofaré Ebenezer Ahenkan Ayôla Akim Adegnika Michael Ramharter Philipp Uhl Gert Fricker Sebastian G. Wicha Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma Malaria Journal Fosmidomycin LC–MS/MS Pharmacokinetics Bioanalysis Malaria |
| title | Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma |
| title_full | Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma |
| title_fullStr | Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma |
| title_full_unstemmed | Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma |
| title_short | Development and application of an LC–MS/MS method for quantification of fosmidomycin in human and rat plasma |
| title_sort | development and application of an lc ms ms method for quantification of fosmidomycin in human and rat plasma |
| topic | Fosmidomycin LC–MS/MS Pharmacokinetics Bioanalysis Malaria |
| url | https://doi.org/10.1186/s12936-025-05489-1 |
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