{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:15:08Z","timestamp":1781615708619,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cystic Fibrosis Switzerland and the Swiss Working Group for Cystic Fibrosis (SWGCF)","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"Cystic Fibrosis Switzerland and the Swiss Working Group for Cystic Fibrosis (SWGCF)","award":["324730_192449"],"award-info":[{"award-number":["324730_192449"]}]},{"name":"Cystic Fibrosis Switzerland and the Swiss Working Group for Cystic Fibrosis (SWGCF)","award":["32003B_179273"],"award-info":[{"award-number":["32003B_179273"]}]},{"name":"SNF","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"SNF","award":["324730_192449"],"award-info":[{"award-number":["324730_192449"]}]},{"name":"SNF","award":["32003B_179273"],"award-info":[{"award-number":["32003B_179273"]}]},{"name":"SNF","award":["2022"],"award-info":[{"award-number":["2022"]}]},{"name":"SNF","award":["324730_192449"],"award-info":[{"award-number":["324730_192449"]}]},{"name":"SNF","award":["32003B_179273"],"award-info":[{"award-number":["32003B_179273"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cystic fibrosis (CF) is a life-threatening disorder caused by mutations in the CFTR gene, leading to defective chloride ion transport and thickened mucus in the respiratory and gastrointestinal systems. CFTR modulators, including ivacaftor, lumacaftor, tezacaftor, and elexacaftor, have improved patient outcomes, but interindividual pharmacokinetic variability and potential drug\u2013drug interactions require therapeutic drug monitoring (TDM) for optimal efficacy and safety. In this context, a liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) method has been developed and validated for the simultaneous quantification of CFTR modulators and their major active metabolites in human plasma to support pharmacokinetic studies and routine TDM. The multiplex LC-MS\/MS assay was established using plasma protein precipitation, followed by chromatographic separation on an Xselect HSS T3 (Waters\u00ae) column and positive electrospray ionization mode detection. The method was validated based on FDA and EMA guidelines for specificity, linearity, accuracy (89.8\u2013107.8%), repeatability (1.1\u20138.1%), intermediate fidelity (1.3\u201310.9%), matrix effects, and stability, demonstrating a robust performance with excellent precision and accuracy. International interlaboratory comparisons confirmed the reliability of the assay. The developed method can be applied for the clinical monitoring of caftors\u2019 plasma concentrations and preliminary data suggest that it can also be applied to alternative matrices, such as breast milk. This method will serve to characterize caftors\u2019 pharmacokinetic variability and monitor drug\u2013drug interactions to further refine personalized dosing strategies and enhance precision medicine treatments for patients with CF.<\/jats:p>","DOI":"10.3390\/molecules30091866","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:11:48Z","timestamp":1745352708000},"page":"1866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantification of Cystic Fibrosis Drugs (Caftors) in Plasma and Its Application for Therapeutic Monitoring"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-7092","authenticated-orcid":false,"given":"Valentina","family":"D\u2019Atri","sequence":"first","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Corrado","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-7617","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Versace","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana Alves","family":"Saldanha","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-4837","authenticated-orcid":false,"given":"Thomas","family":"Mercier","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-9317","authenticated-orcid":false,"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-4277","authenticated-orcid":false,"given":"Paul","family":"Thoueille","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-9705","authenticated-orcid":false,"given":"Sylvain","family":"Blanchon","sequence":"additional","affiliation":[{"name":"Pediatric Pneumology and Cystic Fibrosis Unit, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-1679","authenticated-orcid":false,"given":"Angela","family":"Koutsokera","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis and CFTR-Related Disorders Center, Division of Pulmonology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vogeser","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, LMU University Hospital, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2312-7050","authenticated-orcid":false,"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-927X","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Girardin","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-2467","authenticated-orcid":false,"given":"Georgia","family":"Mitropoulou","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis and CFTR-Related Disorders Center, Division of Pulmonology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zisis","family":"Balmpouzis","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis and CFTR-Related Disorders Center, Division of Pulmonology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-8757","authenticated-orcid":false,"given":"Isabelle","family":"Rochat","sequence":"additional","affiliation":[{"name":"Pediatric Pneumology and Cystic Fibrosis Unit, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Sauty","sequence":"additional","affiliation":[{"name":"Adult Cystic Fibrosis and CFTR-Related Disorders Center, Division of Pulmonology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Division of Pulmonology, Department of Medicine, Neuch\u00e2tel Hospital Network, 2000 Neuch\u00e2tel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-1325","authenticated-orcid":false,"given":"Laurent Arthur","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-4978","authenticated-orcid":false,"given":"Eva","family":"Choong","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, 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