The rapid detection and identification of the impurities of simvastatin using high resolution sub 2 microm particle LC coupled to hybrid quadrupole time of flight MS operating with alternating high-low collision energy.

The profiling and identification of impurities in raw pharmaceuticals or finished drug product is an essential part of the pharmaceutical manufacturing process. Critical to this process is the ability to confirm known, expected impurities and identify new impurities. LC coupled to electrospray MS is a powerful tool that has been employed for the identification of impurities, natural products, drug metabolites, and proteins. In this study, we show how sub 2 microm porous particle LC has been coupled to hybrid quadrupole orthogonal TOF mass spectrometer to profile and identify the impurities of the common cholesterol lowering drug simvastatin. The hybrid quadrupole TOF mass spectrometer was operated by alternating the collision cell energies to allow for the rapid, facile conformation of the identity of impurities. Using this process it was possible to identify all of the common impurities of simvastatin in a single 10 min run. During the analysis a new impurity of simvastatin was detected and identified as the saturated ring form of simvastatin.