Therapeutic monitoring of chlorpromazine. IV: Comparison of a new high-performance liquid chromatographic method with radioimmunoassays for parent drug and some of its major metabolites.

A new high-performance liquid chromatographic (HPLC) procedure for the simultaneous determination of chlorpromazine and its six metabolites, namely, 7-hydroxy-chlorpromazine, N-monodesmethyl-chlorpromazine, 7-hydroxy-N-monodesmethyl-chlorpromazine, chlorpromazine-sulfoxide, chlorpromazine N-oxide, and N-monodesmethyl-chlorpromazine-sulfoxide, in plasma was developed and compared with four radioimmunoassay (RIA) procedures that measured separately chlorpromazine, 7-hydroxy-chlorpromazine, chlorpromazine-sulfoxide, and chlorpromazine N-oxide. The results of this study for the determination of plasma levels in four healthy volunteers given a 100-mg single oral dose of chlorpromazine hydrochloride demonstrated that in some cases, strong correlations could be found between the plasma levels determined by the HPLC and RIA procedures, whereas in other cases, there was a lack of strong correlation. The discrepancies observed were not only due to nonspecificity of the immunoassay procedures employed, but also to a lack of rigorous specificity of the HPLC procedure in plasma samples from dosed humans. These findings clearly indicate that even a chemical method of analysis, such as HPLC, has its limitations in its application to multianalyte analysis, as is the case with drugs like chlorpromazine.