{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:26:14Z","timestamp":1792463174193,"version":"4.5.0"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clozapine (CLZ) is a key drug in treatment\u2010resistant schizophrenia. Therapeutic drug monitoring (TDM) of CLZ and its metabolites, <jats:italic>N<\/jats:italic>\u2010desmethylclozapine and clozapine <jats:italic>N<\/jats:italic>\u2010oxide, is required to monitor and manage the risks of side effects. Although quantification methods for TDM have been developed for CLZ and its metabolites, they were not sufficiently accurate for the quantification of CLZ owing to the upper limits of the calibration curves. An analytical method using high\u2010performance liquid chromatography\/electrospray ionization tandem mass spectrometry was developed and validated for the simultaneous measurement of CLZ and its metabolites in human plasma. To expand the concentration range of the calibration curves, we used a linear range shift technique using in\u2010source collision\u2010induced dissociation (CID). Using our approach, the linearity and quantitative range were improved compared to those reported by previous studies, and were sufficient for TDM in clinical practice. The intra\u2010 and inter\u2010assay accuracy was 84.6%\u2013114.8%, and the intra\u2010 and inter\u2010assay precisions were \u22649.1% and \u22649.9%, respectively. Moreover, all samples from patients with treatment\u2010resistant schizophrenia were successfully quantified. Therefore, our novel analytical method using in\u2010source CID had the appropriate performance to measure the plasma concentrations of CLZ and its metabolites for TDM in clinical practice.<\/jats:p>","DOI":"10.1002\/bmc.5094","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T05:32:55Z","timestamp":1613626375000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Development of a simultaneous analytical method for clozapine and its metabolites in human plasma using liquid chromatography\/electrospray ionization tandem mass spectrometry with linear range adjusted by in\u2010source collision\u2010induced dissociation"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8807-2417","authenticated-orcid":false,"given":"Toshihiro","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  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