Real time pharmaceutical reaction monitoring by electrospray ion mobility-mass spectrometry

摘要: Abstract Reaction monitoring is a critical step in the synthesis of new drug entities, and many pharmaceutical companies spend significant resources on equipment methods to perform this task. The potential electrospray ion mobility-mass spectrometry (ESI-IMMS) as method for reactions real time demonstrated with reductive amination reaction that commonly used amines discovery but poses problems detection current analytical instrumentation. Data were collected timescale 300 s completion was determined by starting, intermediate product materials during reaction. limits nicotinaldehyde (starting material 1), 4-picolylamine 2), di-(2-picolyl)amine (the product) 0.32, 0.10 0.05 μM, respectively, linear dynamic range more than 2 orders magnitude each analyte. Starting not separated their mobility nitrogen buffer gas, could be gas carbon dioxide. In reduced ( K o ) values starting (nicotinaldehyde, 4-picolylamine, 4-pyridinementhanol) 1.86 cm /Vs value (di-(2-picolyl)amine) 1.69 cm /Vs. dioxide 1.43 cm 1.38 cm respectively. coupling IMS MS enabled hemiacetal complex forming between methanol, limiting availability Thus use conjunction provided information about mechanism would have been possible alone. complexation prevented formation species, presumably due from SM1; however, species formed when concentration increased 10-fold. While either or alone monitor similar reactions, combined ESI-IMMS approach offered complete reaction, demonstrating rapid selective technique aid process control.