Thompson H C, Holder C L
J Chromatogr. 1984 Jan 20;283:251-64. doi: 10.1016/s0021-9673(00)96260-5.
Toxicological evaluation of the antihistamines methapyrilene hydrochloride, pyrilamine maleate, and triprolidine hydrochloride monohydrate using methapyrilene hydrochloride as the positive indicator was investigated as part of a structure-activity relationship study in rats and mice. Prerequisites for the toxicological tests were the development of analytical procedures to certify the dose, homogeneity and stability of the drugs in animal feed and to monitor human urine for possible exposure and to ensure removal of the test agents from wastewater prior to its discharge into the environment. A high-performance liquid chromatographic (HPLC) system was developed using a fluorescence detector for the determination of methapyrilene hydrochloride and pyrilamine maleate in feed at levels as low as 100 ng/g and in human urine as low as 1 ng/g. An HPLC-UV procedure was developed for the determination of triprolidine hydrochloride monohydrate in feed at levels as low as 10 micrograms/g. Data concerning p-values, extraction efficiencies from feed and stability experiments in feed are presented for these antihistamines. A gas chromatographic procedure using a nitrogen-phosphorus detector was also developed for determining the three antihistamines in admixture in wastewater at levels as low as 10 ng/g.
作为大鼠和小鼠构效关系研究的一部分，以盐酸美吡拉敏作为阳性指标，对盐酸美吡拉敏、马来酸氯苯那敏和盐酸曲普利啶一水合物这几种抗组胺药进行了毒理学评估。毒理学试验的前提条件是开发分析程序，以确认药物在动物饲料中的剂量、均匀性和稳定性，监测人体尿液中是否可能接触到药物，并确保在废水排放到环境之前去除试验药物。开发了一种高效液相色谱（HPLC）系统，使用荧光检测器测定饲料中低至100 ng/g的盐酸美吡拉敏和马来酸氯苯那敏，以及人体尿液中低至1 ng/g的含量。开发了一种HPLC-UV方法，用于测定饲料中低至10μg/g的盐酸曲普利啶一水合物。给出了这些抗组胺药的p值、从饲料中的提取效率和饲料中的稳定性实验数据。还开发了一种使用氮磷检测器的气相色谱方法，用于测定废水中低至10 ng/g的三种混合抗组胺药。
