An investigation of the mutagenic activity of salamide – a major impurity of hydrochlorothiazide

Abstract

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.

Keywords:

• Bacterial reverse mutation test
• genotoxic impurities
• hydrochlorothiazide
• mutagenicity
• salamide impurity

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.