Development, Validation and Application of an Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) Method to Determine Cobalt in Apixaban

Elemental impurities in drug products /substances from several sources are often observed; they may be residues or impurities from catalyst required during synthesis or from the material of construction (e. g. , through interactions with processing equipment’s or container/closure systems or by being present in components of the drug substance (Figure No.1). From January 1, 2018, a new guideline ICH Q3D, regarding elemental impurities in drug products became effective published by International Conference on Harmonization. In this article, a case study is represented by developing a selective and highly sensitive Inductive Coupled Plasma Mass Spectrometry (ICP-MS) method for the determination of Elemental impurity in Apixaban drug substance. Determination of Cobalt content in Apixaban by Inductively Coupled Plasma Mass Spectrometer (ICP- MS) is carried out in the present work. A method is developed and the study was performed to support the method precision, accuracy, and Linearity. Specifically, three representative batches of drug substance Apixaban were analyzed and the results were interpreted. The method was found suitable for the intended purpose. The linearity for all the standards was established from 30 % to 150 % of the concentration range (correlation coefficients were found more the 0.99). Similarly, the accuracy at 30 % concentration level was estimated and recoveries were between 70 % and 130 % ( %w/w). The precision of the same preparation was also found within the acceptable limit.