Application of an Untargeted Chemometric Strategy in the Impurity Profiling of Pharmaceuticals: An Example of Amisulpride.

The untargeted chemometric methodology for the impurity profiling of amisulpride pharmaceutical formulations was successfully applied and developed. For this purpose a fast, accurate and specific analytical method was elaborated with the use of ultra high pressure liquid chromatography coupled with high resolution hybrid electrospray ionization quadrupole time of flight mass spectrometer in a fast polarity switching mode. All the obtained chromatographic profiles were aligned and a multivariate chemometric analysis including principal component analysis and partial least square (PLS) was performed. The developed PLS-DA pattern recognition model allowed the identification of all the analyzed pharmaceutical formulations of amisulpride as well as their manufacturers. Additionally, six impurities of amisulpride were identified by the use of MS/MS fragmentation and one of them was found as the main impurity (Imp-1) and can be regarded as the primary impurity "marker" for the analyzed formulations. Furthermore, one new impurity of amisulpride was found and its chemical structure was proposed (4-amino-5-(ethylsulfinyl)-2-methoxy-N-[(1-ethylpyrrolidin-2-yl)methyl]benzamide).