Synthesis and Characterization of Impurities of an Broad- Spectrum Anthelmintic Drug, Albendazole

Abstract

Albendazole ( 1) is a broad-spectrum anthelmintics drug. Albendazole impurity A, 5- (propylthio)-1H-benzimidazol-2-amine (6), impurity B, methyl (5-(propylsulfinyl)- 1H-benzimidazol- 2-yl)carbamate (7), impurity C, methyl (5-(propylsulfonyl)-1H- benzimidazol-2-yl)carbamate (8) and impurity D, 5-(propylsulfonyl)-1H- benzimidazol-2-amine (9) are degradation or metabolic impurities whereas impurity E, methyl 1H-benzoimidazol- 2-yl)carbamate ( 11 ) and impurity F, methyl (5- (methylthio)-1H- benzimidazol-2-yl)carbamate ( 15 ) are process related impurities. All these impurities are listed in European pharmacopoeia. Present work describes the synthesis and characterization of all these six impurities. 2,3 . The principal mode of action for Albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules. Albendazole was first discovered at the SmithKline Animal Health Laboratories in 1972. Impurities can be closely related to the product that is formed during the synthesis of a bulk drug or it can be decomposition product formed during the storage of the drug. The presence of impurities in an active pharmaceutical ingredient (API) can have a significant impact on the quality and safety of the drug products. Therefore, it is necessary to study the impurity profile of the API to be used in the manufacturing of drug substance. International conference on harmonization (ICH) guidelines recommended identifying and characterizing all impurities that are present at a level of 0.10% or more 4,5 .