{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T01:49:00Z","timestamp":1785376140238,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2024"],"award-info":[{"award-number":["RC2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: The combination of ivacaftor, tezacaftor and elexacaftor (ETI) is approved for patients with cystic fibrosis (CF) aged two years and older and at least one F508del mutation in the CFTR gene. Variability in ETI treatment response has been repeatedly reported, and its reasons are unclear and understudied. Objectives: We present a novel liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) method for the rapid and simultaneous quantification of ETI in plasma, dried plasma spots (DPS), and whole blood volumetric absorptive microsampling (VAMS). Methods: The method utilizes a rapid extraction protocol with 200 \u03bcL methanol after the addition of deuterated internal standards. Chromatographic separation was achieved using a reversed-phase Hypersil Gold aQ column (Thermo Fisher Scientific). The method was validated according to ICH (International Council on Harmonisation) guidelines M10 for bioanalytical method validation, demonstrating linearity in the concentration range 0.020\u201312.000 \u00b5g\/mL. It was also proved accurate and reproducible with no matrix effect. This method was applied to anonymized samples from patients undergoing ETI treatment: eight plasma and DPS and five VAMS samples were analyzed. Results: ETI concentrations measured in plasma and DPS were interchangeable, whereas ETI concentrations in VAMS were lower than in plasma, as expected for molecules with high plasma protein binding (99%). A correction factor based on the hematocrit value was used to calculate the equivalent plasma concentration from VAMS concentrations. Conclusions: This method is suitable for pharmacokinetic (PK) studies and could facilitate the centralization of samples to specialized laboratories, supporting multicenter studies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020200","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:47:31Z","timestamp":1738817251000},"page":"200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel LC-MS\/MS Method for the Measurement of Elexacaftor, Tezacaftor and Ivacaftor in Plasma, Dried Plasma Spot (DPS) and Whole Blood in Volumetric Absorptive Microsampling (VAMS) Devices"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-8610","authenticated-orcid":false,"given":"Federica","family":"Pigliasco","sequence":"first","affiliation":[{"name":"Unit of Biochemistry, Pharmacology and Newborn Screening, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1132-1267","authenticated-orcid":false,"given":"Alessia","family":"Cafaro","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Pharmacology and Newborn Screening, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-427X","authenticated-orcid":false,"given":"Sebastiano","family":"Barco","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Pharmacology and Newborn Screening, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2483-5374","authenticated-orcid":false,"given":"Federico","family":"Cresta","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria","family":"Casciaro","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5161-1720","authenticated-orcid":false,"given":"Nicoletta","family":"Pedemonte","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-0262","authenticated-orcid":false,"given":"Francesca","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Pharmacology & Toxicology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 2, 16132 Genoa, Italy"},{"name":"Clinical Pharmacology Unit, EO Ospedali Galliera, Mura Delle Cappuccine, 14, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1916-0963","authenticated-orcid":false,"given":"Carlo","family":"Castellani","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Cangemi","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Pharmacology and Newborn Screening, Central Laboratory of Analysis, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s00018-016-2393-9","article-title":"Cystic fibrosis: A clinical view","volume":"74","author":"Castellani","year":"2017","journal-title":"Cell. 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