{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:42:06Z","timestamp":1789728126131,"version":"4.0.1"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>EAI045 is a tyrosine kinase inhibitor (TKI) that targets the mutant epidermal growth factor receptor (EGFR). It was developed to control resistance to available EGFR TKIs. In this study, a major metabolite of EAI045, (5\u2010fluoro\u20102\u2010hydroxyphenyl)(1\u2010oxo\u20101,3\u2010dihydro\u20102H\u2010isoindol\u20102\u2010yl)acetic acid (PIA), was discovered as a hydrolysis product of the parent drug. A validated assay for both analytes in mouse plasma and tissue homogenates from brain, kidney, liver, lung, spleen, and small intestine with content was set up using LC\u2013MS\/MS. Samples were prepared by protein precipitation with acetonitrile and with PLX4720 as internal standard. Separation was performed on a bridged ethylene hybrid C<jats:sub>18<\/jats:sub> column by gradient elution with 0.1% v\/v formic acid and methanol. Using positive electrospray, detection was performed in selected reaction monitoring mode. A linear calibration range of 2\u20132,000\u2009ng\/ml was used and validated for both analytes. Precision values ranged between 2.0 and 7.5% for EAI045 and between 2.2 and 12.1% for the metabolite, and accuracy values were between 91.1 and 107.6% for EAI045 and between 87.6 and 100.6% for the metabolite. Both analytes were sufficiently stable under the relevant analytical conditions. Finally, the assay was applied to analyze mouse plasma and tissue levels in a pharmacokinetic study in FVB\/NRj wild\u2010type female mice treated with oral EAI045.<\/jats:p>","DOI":"10.1002\/bmc.5457","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T03:29:33Z","timestamp":1658287773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bioanalytical assay for the quantification of the tyrosine kinase inhibitor EAI045 and its major metabolite PIA in mouse plasma and tissue homogenates using liquid chromatography\u2013tandem mass spectrometry"],"prefix":"10.1002","volume":"36","author":[{"given":"M. Merve","family":"Susam","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute, CX  Amsterdam The Netherlands"},{"name":"Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University, CG  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute, CX  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred H.","family":"Schinkel","sequence":"additional","affiliation":[{"name":"Division of Pharmacology The Netherlands Cancer Institute, CX  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos H.","family":"Beijnen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology The Netherlands Cancer Institute, CX  Amsterdam The Netherlands"},{"name":"Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht University, CG  Utrecht The Netherlands"},{"name":"Division of Pharmacology The Netherlands Cancer Institute, CX  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-7937","authenticated-orcid":false,"given":"Rolf W.","family":"Sparidans","sequence":"additional","affiliation":[{"name":"Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacology Utrecht University, CG  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.863"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105583"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100103"},{"key":"e_1_2_10_5_1","unstructured":"European Medicines Agency. 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