How reliable are reported plasma clozapine levels?

Many practitioners use plasma levels to determine the optimum dosage of clozapine. The aim of this study was to determine the intra- and interlaboratory accuracy in assaying samples of clozapine dissolved in human plasma.

Three samples were sent to one laboratory to obtain an initial determination of accuracy (phase I). Then samples of clozapine dissolved in human plasma were prepared at concentrations of 140, 310 and 580 ng/mL and dispatched on dry ice to 10 assaying centres in Australia and New Zealand. The results of the survey were analysed and posted to each centre (phase II). The programme was repeated using concentrations of 160, 380 and 640 ng/mL (phase III). Samples prepared in purified water and freeze-dried samples were also dispatched.

In phase II there were two centres with results significantly different from the mean. In phase III all the centres returned concordant results. There was a high level of consistency in the measurement of samples with a maximum coefficient of variation of 0.16. The concentrations determined by the centres, however, were significantly lower than the nominal concentrations of the prepared solutions.

Clinicians in Australia and New Zealand who wish to know their patients' plasma-clozapine levels can be confident that the result of the assay is unlikely to vary with the choice of centre or the operator who performs the assay.