{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T11:19:14Z","timestamp":1781349554086,"version":"3.54.1"},"reference-count":9,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["848016010"],"award-info":[{"award-number":["848016010"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pemetrexed is an antifolate drug approved for the treatment of non\u2010small\u2010cell lung cancer and mesothelioma. Assessing pemetrexed pharmacokinetics after administration of a microdose (100\u2009\u03bcg) may facilitate drug\u2013drug interaction and dose individualization studies with cytotoxic drugs, without causing harm to patients. Therefore, a highly sensitive bioanalytical assay is required.<\/jats:p><jats:p>A reversed\u2010phase ultra\u2010high performance liquid chromatography method was developed to determine pemetrexed concentrations in human ethylenediaminetetraacetic acid\u2013plasma after microdosing. [<jats:sup>13<\/jats:sup>C<jats:sub>5<\/jats:sub>]\u2010Pemetrexed was used as the internal standard. The sample preparation involved solid\u2010phase extraction from plasma. Detection was performed using MS\/MS in a total run time of 9.5\u00a0min.<\/jats:p><jats:p>The assay was validated over the concentration range of 0.0250\u201325.0\u00a0\u03bcg\/L pemetrexed. The average accuracies for the assay in plasma were 96.5 and 96.5%, and the within\u2010day and between\u2010day precision in coefficients of variations was &lt;8.8%. Extraction recovery was 59\u2009\u00b1\u20091 and 55\u2009\u00b1\u20095% for pemetrexed and its internal standard. Processed plasma samples were stable for 2\u00a0days in a cooled autosampler at 10\u00b0C.<\/jats:p><jats:p>The assay was successfully applied in a pharmacokinetic curve, which was obtained as a part of an ongoing clinical microdosing study.<\/jats:p>","DOI":"10.1002\/bmc.5277","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T23:54:08Z","timestamp":1636156448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Highly sensitive quantification of pemetrexed in human plasma using UPLC\u2010MS\/MS to support microdosing studies"],"prefix":"10.1002","volume":"36","author":[{"given":"Eleonora W. J.","family":"van Ewijk\u2010Beneken Kolmer","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marga J. A.","family":"Teulen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene J.","family":"Boosman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology Antoni van Leeuwenhoek\u2014The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"de Rouw","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Pharmacy Jeroen Bosch Hospital, 's\u2010Hertogenbosch  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus A.","family":"Burgers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology Antoni van Leeuwenhoek\u2014The Netherlands Cancer Institute  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-8201","authenticated-orcid":false,"given":"Rob","family":"ter Heine","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"EMA. (2011). Guideline on bioanalytical method validation. Available at:http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2011\/08\/WC500109686.pdf. Accessed 30 January 2021."},{"key":"e_1_2_10_3_1","unstructured":"FDA. (2018) Guidance for Industry: Bioanalytical method validation. Available at:https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf. Accessed January 30th."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2016.06.029"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.08.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0077-5"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2017-1104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy275"},{"key":"e_1_2_10_9_1","volume-title":"PubChem Pemetrexed compound summary","year":"2019"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00769-x"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.5277","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:52:17Z","timestamp":1760043137000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.5277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,22]]},"references-count":9,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/bmc.5277"],"URL":"https:\/\/doi.org\/10.1002\/bmc.5277","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,22]]},"assertion":[{"value":"2021-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5277"}}