Pt. Mccarthy et al., MEASUREMENT OF CLOZAPINE AND NORCLOZAPINE IN PLASMA SERUM BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ULTRAVIOLET DETECTION, BMC. Biomedical chromatography, 9(1), 1995, pp. 36-41
A simple method for the measurement of clozapine and its N-desmethyl m
etabolite in human plasma or serum by high performance liquid chromato
graphy is described. An internal standard (aqueous nortriptyline, 4 mg
/L) (50 mu L) and Tris buffer (2 mol/L, pH 10.6) (100 mu L) are added
to plasma/serum (200 pi) and the analytes and internal standard extrac
ted into methyl tert-butyl ether (200 mu L). The extracts are analysed
on a 150 mm column containing Spherisorb S5SCX using methanol contain
ing ammonium perchlorate (35 mmol/L, pH 6.7) as eluent at a flow rate
of 1.5 mL/min. Detection is by ultraviolet absorption (215 nm). The li
mit of detection is better than 0.05 mg/L for both analytes and the in
tra-assay precision (CV) for clozapine and norclozapine was 5.3 and 7.
3% at 0.5 mg/L and 2.6 and 2.8% at 1.5 mg/L, respectively. The method
can be applied to the measurement of these compounds in plasma after a
cute overdosage, for the assessment of compliance in patients apparent
ly refractory to therapy and to identify interactions between clozapin
e and other neuroleptic and antidepressant drugs which may effect toxi
city.