Investigational Study of DASATINIB N-Oxide Impurity in Different Diluents.

Abstract

Dasatinib is an aminopyrimidine used as an inhibitor of multiple tyrosine kinases in two different formulations an immediate-release tablet and a powder for oral suspension. It shows a very low pH-dependent solubility in aqueous solutions and higher solubility in organic solvents. The solubility plays an essential role in analytical methodology to establish the purity, potency, safety and efficacy of any drug product as a diluent. Also, extraction of active drug substance with a suitable diluent from matrix composition is crucial for any analytical method development. However, a diluent optimization study during the method development of related substances for the drug product reveals that the Piperazine ring presented in Dasatinib is susceptible to oxidation and forms an N-oxide impurity. The impurity formation is due to the micro oxidic properties of the solvent used as a diluent which is inducing an oxidation reaction. Therefore, a comprehensive investigative study was conducted to optimize the diluent by limiting N-Oxide generation.