Radioimmunoassay for trimeprazine in human plasma.

Antisera to trimeprazine were raised in New Zealand white rabbits to an immunogen synthesized by covalent linkage of bovine serum albumin to N-(2-carboxyethyl)desmethyltrimeprazine. By use of an antiserum, a radioimmunoassay for trimeprazine was developed that is able to quantitate 0.38 ng/ml-1 in a 200 microliter plasma sample with a coefficient of variation of approximately 12%. The antiserum did not cross-react with the supposedly pharmacologically inactive metabolite trimeprazine sulfoxide; however, the cross-reactivity with the supposedly active metabolite N-desmethyltrimeprazine is significant (49%). The radioimmunoassay was able to measure the drug and/or N-desalkyl metabolites in plasma samples obtained as late as 24 hr following administration of a single oral dose (10mg) of trimeprazine tartrate. Analysis of the same plasma samples by a published high-performance liquid chromatographic procedure gave values much lower than those obtained by the radioimmunoassay, indicating the N-desalkyl metabolites are produced significantly after trimeprazine oral administration.

Radioimmunoassays for phenothiazine drugs and their major metabolites in plasma.

Radioimmunoassay procedures have been developed for some phenothiazine drugs and their major metabolites which are capable of quantitating 0.3 ng/ml or less in a 200 microliter plasma sample with a coefficient of variation less than 3%. They were developed with a view to their use in pilot investigations of plasma level versus clinical response correlations. The development of the procedures for trifluoperazine are described in this workshop. Antisera to trifluoperazine have been raised in New Zealand white rabbits to several different types of immunogens, where there was variation in the length and nature of the N-10 side chain attached to the phenothiazine nucleus, as well as in the number of hapten residues coupled to bovine serum albumin. An improved radioimmunoassay for trifluoperazine has been developed which showed cross-reactivities to the N-desmethyl and 7-hydroxy metabolites of trifluoperazine of the order of 12 and 11%, respectively, in comparison to the 26 and 24% cross-reactivity, respectively, for the same metabolites by a previously reported procedure.