Thompson H C, Holder C L, Bowman M C
J Chromatogr Sci. 1982 Aug;20(8):373-80. doi: 10.1093/chromsci/20.8.373.
Doxylamine succinate, a drug used as a sleep-inducing agent, an antihistamine, and in a therapeutic formulation taken by pregnant women as an antinauseant, was scheduled for toxicological evaluation as part of a structure activity relationship study, with rats and mice, because a deficiency of such data exists with regard to many antihistamines. Analytical chemical procedures that ensure proper concentration, homogeneity, and stability of the drug in dosed feed, as well as the safety of personnel and the environment, were prerequisites for the toxicological tests. GC methods using a rubidium-sensitized nitrogen detector were developed for analysis of doxylamine succinate in animal feed, human urine, and wastewater at levels as low as 1 ppm, 100 ppb, and 100 ppb, respectively. Sample extracts were cleaned up by liquid-liquid partitioning, followed by additional cleanup on a column of silica gel. Data are presented concerning the stability of the drug in animal feed, extraction efficiencies, and the use of the silica gel cleanup column to separate the caffeine interference from doxylamine in extracts of human urine. Partition values and ancillary data concerning analysis of the drug in feed, by HPLC at levels as low as 10 ppm, are also reported.
琥珀酸多西拉敏是一种用作催眠剂、抗组胺药的药物，在孕妇服用的治疗配方中用作止吐剂。由于许多抗组胺药缺乏此类数据，因此作为构效关系研究的一部分，计划对大鼠和小鼠进行毒理学评估。确保药物在给药饲料中的浓度、均匀性和稳定性以及人员和环境安全的分析化学程序是毒理学试验的先决条件。开发了使用铷敏化氮检测器的气相色谱方法，用于分别分析动物饲料、人尿和废水中低至1 ppm、100 ppb和100 ppb水平的琥珀酸多西拉敏。样品提取物通过液液分配进行净化，然后在硅胶柱上进行进一步净化。给出了关于药物在动物饲料中的稳定性、提取效率以及使用硅胶净化柱分离人尿提取物中咖啡因对多西拉敏干扰的数据。还报告了通过高效液相色谱法在低至10 ppm水平下分析饲料中药物的分配值和辅助数据。
