Acta Pharm. 54 (2004) 163-176

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

MILENA JADRIJEVIC-MLADAR TAKAC^1*, DRAZEN VIKIC TOPIC² and TIHANA GOVORCINOVIC¹

mladar@pharma.hr

¹Faculty of Pharmacy and Biochemistry, University of Zagreb, 10 000 Zagreb, Croatia
²NMR Centre, Institute Rudjer Boskovic, POB 180, 10002 Zagreb, Croatia

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 O…HO 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