Use of online sequential segmented heart cutting modulation and orthogonality approach for determination of isomeric impurity profile of a drug molecule using parallel 2-dimensional mass spectroscopy

Abstract

Determination of impurity profile including chiral and achiral impurities is challenging as well as time consuming while analysis of the active moiety. With the recent evolution of 2-Dimensional separation modes, significant improvement can be made for simultaneous determination of both achiral and chiral impurities in a single set-up. Herein, the present work represents example of how both chiral and achiral impurities can be determined simultaneously. To represent the work, galantamine HBr was selected as the active moiety since it has achiral as well as many chiral impurities. Further, a 1D UPLC method with shorter runtime was developed to determine the achiral impurities and simultaneous heart cutting approach was used to cut the impurities and active compound and transfer to 2D chiral setup to separate out chiral impurities and perform its quantification. Both methods were proven to be orthogonal to each other with orthogonality factor of 0.241.