Publication
Title
Retrospective evaluation of therapeutic drug monitoring of clozapine and norclozapine in Belgium using a multidrug UHPLC-MS/MS method
Author
Abstract
Objective Clozapine is an atypical antipsychotic with a narrow therapeutic range and serious toxic side effects. According to AGNPTDM consensus guidelines, therapeutic drug monitoring (TDM) of clozapine and its metabolite norclozapine is strongly recommended. 330 serum samples, sent to the toxicological laboratory of Ziekenhuis Netwerk Antwerpen for monitoring of clozapine, were tested with a new ultra-high performance liquid chromatographytandem mass spectrometric method (UHPLCMS/MS). The aim of this research was to evaluate this method for TDM of clozapine and norclozapine, but also to determine other antipsychotics present in these serum samples. Design and methods Serum samples were taken just prior to the morning dose of the antipsychotic (trough concentration). All samples were, after a simple liquidliquid extraction with methyl t-butylether, analyzed using a fully validated UHPLCMS/MS method which is able to quantitate 16 different antipsychotics and 8 of their major metabolites. Serum concentrations were compared with the therapeutic ranges as defined by the AGNPTDM guidelines. Results For clozapine, only 22.3% of the serum concentrations were within the therapeutic range of 350600 ng/mL, while 67.9% of the concentrations were below 350 ng/mL. For norclozapine, 68.2% of the serum samples were within the therapeutic range of 100600 ng/mL. The mean clozapine:norclozapine ratio was 1.7 (SD 0.8). 218 of the 330 serum samples contained other antipsychotics than clozapine. Only 52.5% of these concentrations were within the proposed range. Conclusion This retrospective study highlights the importance of TDM for clozapine and other APs, since many patients show suboptimal serum concentrations.
Language
English
Source (journal)
Clinical biochemistry. - Toronto, Ont.
Publication
Toronto, Ont. : 2014
ISSN
0009-9120
Volume/pages
47:18(2014), p. 336-339
ISI
000346125500017
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 01.12.2014
Last edited 21.09.2017
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