ABSTRACT
OBJECTIVE: To establish the national reference standards of sulfadimidine impurities thus to provide guarantee for improving the standard of quality control of sulfadiazine in China. METHODS: First, the structures of sulfadimidine impurities A and E were validated by infrared spectrocopy, mass spectrum and nuclear magnetic resonance method. Then, the purities of impurities A and E were determined using the method of related substance test for sulphadiazine in the European Pharmacopoeia (version 9.0),their water content and residue on ignition were determined as well. The contents of sulfadimidine impurities A and E were determined by using mass balance method. Meanwhile, external standard method and nuclear magnetic quantitative method were used to calculate the content, which were mutually verified with the mass balance method. Finally, the correction factors of sulfadiazine impurities A and E at 241 nm were determined using standard curve method. RESULTS: The structures of sulfadimidine impurities A and E were confirmed, and the contents of impurities A and E were 99.1% and 98.7%, respectively, which were calculated by mass balance method. The results were consistent with those obtained from external standard method and nuclear magnetic quantification method. The correction factors of impurities A and E to sulfadimidine were 0.97 and 0.63, respectively. CONCLUSION: The first batch of national standard substances of sulfadimidine impurities A and E were established successfully.