{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:32:34Z","timestamp":1760661154115,"version":"build-2065373602"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011851","name":"Kom op tegen Kanker","doi-asserted-by":"publisher","award":["001850494"],"award-info":[{"award-number":["001850494"]}],"id":[{"id":"10.13039\/501100011851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Mass Spectrom"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Gemcitabine (dFdC), an effective chemotherapeutic for non\u2013small cell lung cancer (NSCLC), acts through its active metabolite, dFdCTP. Its current pharmacokinetics (PK) knowledge is based on intravenous infusion, which does not represent locoregional administration. In contrast, locoregional studies focus on dFdC, neglecting the role of dFdU (inactive) and dFdCTP, limiting our lung\u2010specific PK insights. Existing dFdCTP assays require lengthy runs and complex protocols, reducing their translatability for large\u2010scale studies. This study presents an ultra\u2010high\u2010performance liquid chromatography tandem mass spectrometry (UHPLC\u2013MS\/MS) method to quantify dFdC, dFdU, and dFdCTP in pig lung tissue and plasma, improving gemcitabine's PK assessment following both systemic and locoregional therapies. A high\u2010throughput UHPLC\u2013MS\/MS method was developed and validated for the quantification of dFdC, dFdU, and dFdCTP in pig plasma and lung tissue. Protein precipitation was used, followed by chromatographic separation on a Luna Omega Polar C18 column with a 4\u2010min run time. Linearity was established over the ranges: 0.5\u2013400.0\u2009\u03bcg\/mL (plasma) and 0.5\u2013400.0\u2009\u03bcg\/g (lung tissue). It demonstrated robust accuracy, precision, and selectivity with minimal carryover and negligible matrix effects. Stability was confirmed for 4\u2009h at 4\u00b0C, 40\u00b0C, and on the autosampler. The method's applicability was verified in study samples treated with a 30\u2010min intravenous gemcitabine (1.25\u2009g\/m<jats:sup>2<\/jats:sup>) infusion. This UHPLC\u2013MS\/MS assay overcomes previous methodological limitations by reducing run time and simplifying sample preparation. Its robustness to quantify dFdC, dFdU, and dFdCTP in pig plasma and lung tissue has been confirmed, providing a valuable tool for future PK studies with locoregional therapies for NSCLC.<\/jats:p>","DOI":"10.1002\/jms.5174","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T11:39:43Z","timestamp":1758022783000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative UHPLC\u2013MS\/MS Analysis of Gemcitabine and Its Active and Inactive Metabolites in Pig Plasma and Lung Tissue in Preparation of Locoregional Therapies for Non\u2013Small Cell Lung Cancer"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8739-5725","authenticated-orcid":false,"given":"Erik","family":"Claes","sequence":"first","affiliation":[{"name":"ASTARC (Antwerp Surgical Training, Anatomy and Research Centre) University of Antwerp  Wilrijk Belgium"},{"name":"Department of Thoracic and Vascular Surgery University Hospital Antwerp  Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeroen\u00a0M.\u00a0H.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"ASTARC (Antwerp Surgical Training, Anatomy and Research Centre) University of Antwerp  Wilrijk Belgium"},{"name":"Department of Thoracic and Vascular Surgery University Hospital Antwerp  Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Th\u00e9r\u00e8se\u00a0S.","family":"Lapperre","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital Antwerp  Edegem Belgium"},{"name":"LEMP (Laboratory of Experimental Medicine and Pediatrics) University of Antwerp  Wilrijk Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Van\u00a0Daele","sequence":"additional","affiliation":[{"name":"BioNotus CommV  Niel Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia","family":"Alves","sequence":"additional","affiliation":[{"name":"BioNotus CommV  Niel Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"BioNotus CommV  Niel Belgium"},{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stijn\u00a0E.","family":"Verleden","sequence":"additional","affiliation":[{"name":"ASTARC (Antwerp Surgical Training, Anatomy and Research Centre) University of Antwerp  Wilrijk Belgium"},{"name":"Department of Thoracic and Vascular Surgery University Hospital Antwerp  Edegem Belgium"},{"name":"Department of Pulmonology University Hospital Antwerp  Edegem Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"unstructured":"Gemzar\u2014Article 30 referral\u2014Annex I II IIIEuropean Medicine Agency2008.","key":"e_1_2_8_2_1"},{"unstructured":"Food and Drug Administration1996GEMZAR\u00ae (GEMCITABINE HCl) FOR INJECTION.","key":"e_1_2_8_3_1"},{"doi-asserted-by":"publisher","key":"e_1_2_8_4_1","DOI":"10.1016\/S1368-7646(02)00002-X"},{"doi-asserted-by":"publisher","key":"e_1_2_8_5_1","DOI":"10.3389\/fphar.2023.1274692"},{"doi-asserted-by":"publisher","key":"e_1_2_8_6_1","DOI":"10.1111\/bcp.13557"},{"doi-asserted-by":"publisher","key":"e_1_2_8_7_1","DOI":"10.1016\/j.bcp.2006.07.036"},{"doi-asserted-by":"publisher","key":"e_1_2_8_8_1","DOI":"10.2174\/156800911793743600"},{"doi-asserted-by":"publisher","key":"e_1_2_8_9_1","DOI":"10.1158\/1535-7163.MCT-08-0137"},{"doi-asserted-by":"publisher","key":"e_1_2_8_10_1","DOI":"10.1200\/JCO.2009.24.4491"},{"doi-asserted-by":"publisher","key":"e_1_2_8_11_1","DOI":"10.1016\/j.lungcan.2008.06.009"},{"issue":"1","key":"e_1_2_8_12_1","first-page":"1","article-title":"Selective Pulmonary Artery Perfusion With Blood Flow Occlusion Delivers Concentrated Levels of Chemotherapy to Ipsilateral Hilar and Mediastinal Lymph Nodes","volume":"5","author":"Sparks P. 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