{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:39:32Z","timestamp":1787009972118,"version":"build-2736575974"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Plasma and serum are often used interchangeably for therapeutic drug monitoring (TDM) purposes, and concentrations of some drugs are reported to be lower in serum than in plasma when collected into blood collection tubes containing a gel separator. TDM is recommended for clozapine, although few studies have compared concentrations between plasma and serum. Therefore, we investigated the comparability of dipotassium ethylenediaminetetraacetic acid human plasma and serum from blood collection tubes containing a gel separator for the measurement of clozapine and norclozapine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Whole blood from patients (N = 93) prescribed clozapine was collected into a polypropylene Vacuette dipotassium ethylenediaminetetraacetic acid\u2013containing blood collection tube (Greiner Bio-One), and a polypropylene Vacuette serum separator blood collection tube (Greiner Bio-One) containing a clotting activator (silica particles) and a polymer gel.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Mean clozapine concentrations were significantly (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2264 0.05) lower in serum (0.37 mg\/L) than in plasma (0.39 mg\/L), as were concentrations of norclozapine (0.17 and 0.18 mg\/L, respectively). Bland\u2013Altman plots indicated mean serum clozapine and norclozapine were 0.018 mg\/L (5.3%) and 0.004 mg\/L (3.6%), respectively, lower in serum than plasma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Despite the finding that clozapine and norclozapine were significantly higher in plasma than in serum when obtained from blood collected into Vacuette serum separator collection tubes, this difference is insignificant in the clinical interpretation of clozapine and norclozapine TDM results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000478","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T09:29:29Z","timestamp":1513157369000},"page":"148-150","source":"Crossref","is-referenced-by-count":11,"title":["Clozapine and Norclozapine Concentrations in Paired Human Plasma and Serum Samples"],"prefix":"10.1097","volume":"40","author":[{"given":"Simon A.","family":"Handley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart W.","family":"Silk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle S.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krithika","family":"Subramaniam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Flanagan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.clinbiochem.2009.10.001","article-title":"Impact of blood collection devices on clinical chemistry assays","volume":"43","author":"Bowen","year":"2010","journal-title":"Clin Biochem."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"31","DOI":"10.11613\/BM.2014.006","article-title":"Interferences from blood collection tube components on clinical chemistry assays","volume":"24","author":"Bowen","year":"2014","journal-title":"Biochem Med (Zagreb)"},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1097\/FTD.0b013e3181dad1fb","article-title":"Plasma clozapine, norclozapine, and the clozapine:norclozapine ratio in relation to prescribed dose and other factors: data from a therapeutic drug monitoring service, 1993-2007","volume":"32","author":"Couchman","year":"2010","journal-title":"Ther Drug Monit."},{"key":"R4-20230814","article-title":"AGNP consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017","author":"Hiemke","year":"2017","journal-title":"Pharmacopsychiatry"},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1097\/00007691-199906000-00014","article-title":"Clozapine monitoring: plasma or serum levels?","volume":"21","author":"Kaladjian","year":"1999","journal-title":"Ther Drug Monit."},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1097\/FTD.0b013e31815f4e72","article-title":"Clozapine and norclozapine concentrations in serum and plasma samples from schizophrenic patients","volume":"30","author":"Hermida","year":"2008","journal-title":"Ther Drug Monit."},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1365-2125.1998.00822.x","article-title":"Pharmacokinetics of clozapine and its metabolites in psychiatric patients: plasma protein binding and renal clearance","volume":"46","author":"Schaber","year":"1998","journal-title":"Br J Clin Pharmacol."},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.forsciint.2013.03.021","article-title":"Stability of some atypical antipsychotics in human plasma, haemolysed whole blood, oral fluid, human serum and calf serum","volume":"229","author":"Fisher","year":"2013","journal-title":"Forensic Sci Int."},{"key":"R10-20230814","article-title":"Ultra-fast LC-MS\/MS in therapeutic drug monitoring: quantification of clozapine and norclozapine in human plasma","author":"Couchman","year":"2017","journal-title":"Drug Test Anal."},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1211\/0022357043969","article-title":"Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds-implications for pharmacokinetics of selected substrates","volume":"8","author":"El Ela","year":"2004","journal-title":"J Pharm Pharmacol."},{"key":"R12-20230814","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cca.2016.08.014","article-title":"Where clinical chemistry meets medicinal chemistry. Systematic analysis of physico-chemical properties predicts stability of common used drugs in gel separator serum tubes","volume":"462","author":"Steuer","year":"2016","journal-title":"Clin Chim Acta."},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/ajcp\/101.4.456","article-title":"Absorption of therapeutic drugs by barrier gels in serum separator blood collection tubes. Volume- and time-dependent reduction in total and free drug concentrations","volume":"4","author":"Dasgupta","year":"1994","journal-title":"Am J Clin Pathol."},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/00007691-200008000-00011","article-title":"Time-dependent absorption of therapeutic drugs by the gel of the Greiner Vacuette blood collection tube","volume":"4","author":"Dasgupta","year":"2000","journal-title":"Ther Drug Monit."},{"key":"R15-20230814","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/00007691-198612000-00019","article-title":"Preparation of serum and plasma samples for determination of tricyclic antidepressants: effects of blood collection tubes and storage","volume":"4","author":"Nyberg","year":"1986","journal-title":"Ther Drug Monit."},{"key":"R16-20230814","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.cca.2011.08.037","article-title":"Influence of separator gel in Sarstedt S-Monovette\u00ae serum tubes on various therapeutic drugs, hormones, and proteins","volume":"413","author":"Schouwers","year":"2012","journal-title":"Clin Chim Acta."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201802000-00019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T15:04:17Z","timestamp":1751123057000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201802000-00019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000478","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2018,2]]}}}