Bioequivalence of two thorazine tablet formulations using radioimmunoassay and gas chromatographic-mass spectrometric methods.

Two analytical methods for the analysis of chlorpromazine (CPZ), a radioimmunoassay (RIA) and a GLC-MS method, were compared in a bioequivalence study of two CPZ tablet formulations (Thorazine: film coated and sugar coated). Thirty-six nonsmoking, healthy, male volunteers completed the study. Each subject ingested single doses (2 x 25 mg) of the test (T) and the reference (R) formulations in a two-way crossover design with a two-week drug-free interval between doses. Following each administration, plasma concentrations of CPZ were monitored over a period of 24 h by both RIA and GLC-MS methods. Plasma concentrations and pharmacokinetic parameters determined by either analytical method showed wide intersubject variation, with the GLC-MS data showing relatively higher magnitude of intersubject variation than the RIA data. In general, plasma concentrations measured by RIA were significantly different from those measured by GLC-MS (paired t tests: p less than 0.0001). As indicated by the regression analysis, concentrations determined by RIA were 1.3-1.4 times higher than those determined by GLC-MS. There were strong and significant correlations between the two methods for both T and R (r greater than 0.75: p less than 0.0001). Similar statistical relationships were found between the plasma concentrations of CPZ determined by the two methods at each sampling time and the bioequivalence parameters area under the plasma level versus time curves up to the last measurable concentration (AUCt0) and the maximum plasma concentration (Cmax).(ABSTRACT TRUNCATED AT 250 WORDS)