LC-MS/MS profile of an active pharmaceutical ingredient and its impurities in commercial preparation

Abstract

The azithromycin is a semisynthetic derivative of erythromycin A, and commercially produced by a series of chemical reaction involved Beckmann rearrangement followed by reductive methylation. Several azithromycin related compounds (ARCs) have been identified as impurity in the commercial products and the processes. These ARCs probably generated from impure starting material; a mixture of different erythromycin. Literature search revealed that approximately 90 erythromycins had been isolated and characterized so far. In current study, we have identified many new ARCs, including previously reported by detailed LC-MS/MS studies. In this study, first, the structures of ARCs were assumed by probable chemical transformation method; erythromycin A to azithromycin A; and, second, assumed structures of ARCs were confirmed by HRMS within the acceptable ppm error limit (±5 ppm) followed by MS/MS fragmentation to identify the characteristic common ion fragments and by precursor ion scan.