Aim: The aim of this study was to present summary data from a serum clozapine proficiency testing scheme. Methods: Monthly returns submitted to the LGC Standards clozapine and norclozapine proficiency testing scheme between 2012 and 2024 were analyzed. Results: A total of 191 participating laboratories participated, of which 164 reported norclozapine results. From 2013 to 2024, the number of returns per distribution was 85. The proportion of laboratories using liquid chromatography–mass spectrometry increased over time and reached 74% in 2024, while the use of high-performance liquid chromatography decreased. Thirteen distributions contained neither analyte; however, 76 returns (6.8%) reported detectable clozapine concentrations (median 10.4, range 0.01–518.73 mcg L −1 ). In 22 distributions, clozapine concentrations >10 mcg L −1 (median 151.63, range 30.3–2175.25 mcg L −1 ) were detected but reported as “0” or below the lower limit of quantification. Comparable findings were observed for norclozapine. No temporal differences in quantitative performance, assessed using z-scores, were observed between analytical methods. Median clozapine z-scores were further from zero when clozapine alone was measured than when both clozapine and norclozapine were measured. Conclusions: Increased use of liquid chromatography–mass spectrometry was not associated with improved analytical performance for clozapine or norclozapine. Method validation should include assessment of potential interference from metabolites and coadministered drugs. Unexpected results require repeat analysis or repeat sampling when clinically feasible.
Couchman et al. (Fri,) studied this question.