Abstract
A sensitive radioimmunoassay (RIA) procedure was developed to assay for bromperidol levels in human plasma after therapeutic drug administration. The antisera used in the RIA procedure was generated in rabbits against a haloperidol-bovine serum albumin conjugate. Tritiated haloperidol was used as the radioligand in the assay. A single ether extraction of alkalinized plasma was used to separate bromperidol from its more polar metabolites and to reduce assay variability encountered with a direct plasma assay. The lower limit of detection was ~0.5 ng/mL of parent drug in plasma. The assay exhibited within- and between-assay variabilities of ~9 and 14%, respectively. A 103–106% recovery of bromperidol from quality control plasma samples was observed over the concentration range of 1–150 ng/mL. A correlation coefficient of 0.9999 with respect to measured versus expected bromperidol content in the quality control plasma samples was exhibited. Cross-reactivity characteristics of the antisera indicated that dehydrobromperidol could significantly interfere (~25% cross-reactivity) with the RIA procedure. However, biotransformation studies have not suggested this compound as a metabolite of bromperidol. Predose (Cmin) plasma levels of bromperidol in schizophrenic patients maintained on drug therapy are also reported.
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