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

Abstract

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 H_8a, H_8b, 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, H_8a and H_8b 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 methanol-d_4.

Keywords::

• Electrospray ionization mass spectrometry
• Hydrogen-deuterium exchange
• Nuclear magnetic resonance
• Proton pump inhibitors
• Tautomerism