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Secondly, the usefulness of liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) was investigated for simultaneous analysis of orally and intravenously administered imatinib.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Included patients were on a stable daily dose of 400\u00a0mg oral imatinib prior to study participation. On day 1, patients received a 100\u00a0\u03bcg intravenous imatinib-d8 microdose 2.5\u00a0h after intake of the oral dose. Plasma samples were collected for 48\u00a0h. Imatinib and imatinib-d8 concentrations were simultaneously quantified using a validated LC-MS\/MS assay. The absolute bioavailability was calculated by comparing the dose-normalized exposure with unlabeled and stable isotopically labeled imatinib in plasma.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A total of six patients were enrolled. All patients had a history of gastrointestinal stromal tumors (GIST). The median absolute bioavailability of oral imatinib at steady state was 76% (range 44\u2013106%). Imatinib and imatinib-d8 plasma concentrations were quantified in all collected plasma samples, with no samples below the limit of quantification for imatinib-d8.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The absolute bioavailability of imatinib was successfully estimated at steady state plasma pharmacokinetics using the stable isotopically labeled microdose trial design. This study exhibits the use of a stable isotopically labeled intravenous microdose to determine the absolute bioavailability of an oral anticancer agent in patients with LC-MS\/MS as the analytical tool.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00228-020-02888-y","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T09:02:50Z","timestamp":1589878970000},"page":"1075-1082","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Determination of the absolute bioavailability of oral imatinib using a stable isotopically labeled intravenous imatinib-d8 microdose"],"prefix":"10.1007","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-7281","authenticated-orcid":false,"given":"Jeroen","family":"Roosendaal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie L.","family":"Groenland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilde","family":"Rosing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikkie","family":"Venekamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastiaan","family":"Nuijen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwin D. 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