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溴哌利多放射免疫测定法:人体血浆水平

Bromperidol radioimmunoassay: human plasma levels.

作者信息

Tischio J, Hetyei N, Patrick J

出版信息

J Pharm Sci. 1984 Apr;73(4):546-8. doi: 10.1002/jps.2600730428.

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 approximately 0.5 ng/mL of parent drug in plasma. The assay exhibited within- and between-assay variabilities of approximately 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 (approximately 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.

摘要

开发了一种灵敏的放射免疫分析(RIA)方法,用于在给予治疗药物后检测人血浆中的溴哌利多水平。RIA方法中使用的抗血清是在兔子体内针对氟哌啶醇 - 牛血清白蛋白偶联物产生的。氚标记的氟哌啶醇用作该分析中的放射性配体。对碱化血浆进行单次乙醚萃取,以将溴哌利多与其极性更强的代谢物分离,并减少直接血浆分析中遇到的分析变异性。检测下限约为血浆中母体药物0.5 ng/mL。该分析的批内和批间变异率分别约为9%和14%。在1 - 150 ng/mL的浓度范围内,观察到溴哌利多从质量控制血浆样品中的回收率为103 - 106%。质量控制血浆样品中实测与预期溴哌利多含量的相关系数为0.9999。抗血清的交叉反应特性表明,脱氢溴哌利多可显著干扰(交叉反应约25%)RIA方法。然而,生物转化研究并未表明该化合物是溴哌利多的代谢物。还报告了接受药物治疗的精神分裂症患者的溴哌利多给药前(Cmin)血浆水平。

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