Emerce Esra, Cok Ismet, Sari Sibel, Bostanci Omur
a Department of Toxicology, Faculty of Pharmacy , Gazi University , Ankara , Turkey.
b Department of Molecular Biology, Division of Biology, Faculty of Science , Hacettepe University , Ankara , Turkey.
Toxicol Mech Methods. 2016 Nov;26(9):644-649. doi: 10.1080/15376516.2016.1222642. Epub 2016 Oct 28.
Hydrochlorothiazide is a widely used antihypertensive agent and one of its major impurities, salamide (4-amino-6-chlorobenzene-1,3-disulphonamide), has a chemical structure containing a primary amino group, a functional group that has previously been reported to be associated with carcinogenic activity. It is known that hydrochlorothiazide purity is a challenging problem for the pharmaceutical industry. As there were no prior mutagenicity data for the impurity salamide, the aim was to investigate its mutagenicity in this study. Salamide was tested for mutagenic potential in Salmonella typhimurium TA98, TA100, TA 1535, TA 1537, and E. coli WP2 uvrA + E. coli WP2 [pKM101] strains at six different concentrations, the highest concentration being the 5000 μg/plate. In both the presence and absence of the metabolic activation system, no mutagenic activity was observed. Results indicated that salamide should be classified as an ordinary impurity and controlled according to Q3A(R2) and Q3B(R2) guidelines.
氢氯噻嗪是一种广泛使用的抗高血压药物，其主要杂质之一沙酰胺（4-氨基-6-氯苯-1,3-二磺酰胺）的化学结构中含有一个伯氨基，此前有报道称该官能团与致癌活性有关。众所周知，氢氯噻嗪的纯度问题对制药行业来说具有挑战性。由于此前没有关于杂质沙酰胺的致突变性数据，本研究旨在调查其致突变性。在六个不同浓度下对沙酰胺在鼠伤寒沙门氏菌TA98、TA100、TA1535、TA1537以及大肠杆菌WP2 uvrA+和大肠杆菌WP2 [pKM101]菌株中的致突变潜力进行了测试，最高浓度为5000μg/平板。在有和没有代谢激活系统的情况下，均未观察到致突变活性。结果表明，沙酰胺应被归类为普通杂质，并根据Q3A(R2)和Q3B(R2)指南进行控制。
