Mono-(6-sulfinic acid)-Sugammadex: A newly identified cyclodextrin-based oxidative impurity in industrial production

Sugammadex is the first cyclodextrin-based API with a well-known mechanism of action, result of a rational drug design and development. It is a γ-cyclodextrin derivative, substituted only on the primary hydroxyl groups, resulting a single isomer and a symmetric molecule. Due to the complex synthetic and purification procedures, currently there are more than a dozen of identified and characterized process related impurities. As the patent held by the originator (Merck & Co., Inc.) approaches expiration globally, generic manufacturers are likely to develop alternative synthetic pathways, which may lead to an increase in the number of impurities. Mapping and characterizing the impurity profile of Sugammadex is therefore essential to ensure patient safety and maintain drug efficacy. In this paper, we have identified and characterized a novel impurity formed through the oxidation and side-chain cleavage of the sulfide bond.