A Single Quadrupole Compact Mass Spectrometer Enabling Early Stage Synthetic Optimization of Verubecestat (MK-8931)

A low-cost compact mass spectrometer was effectively utilized for identifying and tracking process impurities in the early stage development of a multistep synthetic protocol used to prepare the verubecestat drug substance. Process optimizations were influenced by the type, quantity, and final fate of impurities generated during synthesis. Employing a compact mass spectrometer for impurity identification and tracking served as a guide to redesign synthetic strategies which enabled the minimization or avoidance of undesired side products.