Acta Pharm. 54 (2004) 163-176

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Original research paper  

FT-IR and NMR spectroscopic studies of salicylic acid derivatives. I. Gentisamide -
a metabolite of salicylamide


1Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia
2NMR Centre, Institute Rudjer Boskovic, POB 180, 10002 Zagreb, Croatia
Received April 14, 2004      Accepted August 23, 2004

Gentisamide (GAM, 2,5-dihydroxybenzamide), a minor first-pass metabolite of salicylamide (SAM, 2-hydroxybenzamide), was studied using FT-IR, 1D and 2D homo- and heteronuclear 1H and 13C NMR spectroscopy.
GAM was isolated from human urine eight hours after oral administration of SAM. FT-IR, 1H and 13C NMR spectra unequivocally confirmed the chemical structure of GAM through chemical and substituent shifts, coupling constants and connectivities in COSY, NOESY, HETCOR and HBMC spectra.
From NOESY spectra of GAM in DMSO-d6, it was concluded that the amide protons are oriented toward the ortho-proton at C-6. Obtained results indicate that the presence of the additional phenol group at C-5 in GAM favours the formation of intramolecular hydrogen bonding of the OHO type between C2-OH proton and oxygen atom of the amide group.

Keywords: gentisamide, NSAID, salicylamide, biotransformation, FT-IR, 1D and 2D homo- and heteronuclear 1H and 13C NMR