BIOEQUIVALENCE OF 2 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 × 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 < 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>0.75: p<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 (AUC ot) and the maximum plasma concentration (Cmax). Bioequivalence parameters AUC ot, AUC ot, and (Cmax). determined separately from the data obtained by the two methods for the two formulations were examined by analyses of variance (ANOVA) and other criteria and tests for bioequivalence. Results of ANOVA, confidence intervals of test/reference ratios of AUC ot, AUC ox, and Cmax, and statistical tests for bioequivalence indicated that, except for Cmax by GLC‐MS, data generated by both methods indicated bioequivalence of the two formulations (i.e., test/reference ratio was within 100 ± 20%). The experiments suggest that despite significant differences between the absolute plasma concentration values obtained, both methods yielded data for the two formulations which demonstrated that they were bioequivalent. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company