Selective scavenging of the genotoxic impurity methyl p-toluenesulfonate from pharmaceutical formulations

The present study describes an easy and efficient approach for the removal of methyl p-toluenesulfonate, a potentially genotoxic impurity (GTI) from a model active pharmaceutical ingredient (API), 21-chlorodiflorasone. For this purpose, several polystyrene–divinylbenzene based and silica based scavengers were tested and the scavengers which showed the highest removal efficiency and selectivity were chosen for further evaluations. The time course of GTI and API scavenging and also the capacities of different scavengers were studied in this paper. The best GTI removal performance and selectivity was obtained with silica based Si-Trisamine and macroporous polystyrene–divinylbenzene based MP-Trisamine, both leading to 100% methyl p-toluenesulfonate removal with no loss of 21-chlorodiflorasone. Non-specifically bound API could be recovered quantitatively by using 2-propanol:THF (1:1).

► Removal of methyl p-toluenesulfonate can be achieved with a simple scavenging approach.
► Scavengers behave additionally as ion exchangers.
► Scavengers bind p-toluenesulfonic acid formed during the scavenging reaction.
► Complete API recovery from the scavengers can be achieved with a wash step.