Characterization of 8-Deuterium Substituted Proton Pump Inhibitors by Nuclear Magnetic Resonance and Electrospray Ionization Mass Spectrometry

Nuclear magnetic resonance (NMR) was employed to characterize the hydrogen-deuterium exchange for the proton pump inhibitors pantoprazole sodium, esomeprazole sodium, rabeprazole sodium, lansoprazole, and ilaprazole in methanol-d4. The results showed that the 1H and 13C signals of 8-CH2 (labeled as H8a, H8b, and C8) next to the sulfinyl (S˭O) group of the proton pump inhibitors decreased significantly. Electrospray ionization mass spectrometry showed the presence of deuterated products. Basing on the NMR data, H8a and H8b of proton pump inhibitors were more active for the hydrogen-deuterium exchange. The most significant parameter governing the exchange was the salt-formation of the benzimidazole group. Therefore, the influence of salt-formation on hydrogen-deuterium exchange was characterized for ilaprazole; replacement of NH by N–Na on the benzimidazole group accelerated the exchange process. Tandem mass spectrometry showed that CH˭S–OH was formed by tautomerism involving sulfinyl and CH2 groups in meth...