ASSIGNMENT OF THE 750 MHZ H-1-NMR RESONANCES FROM A MIXTURE OF TRANSACYLATED ESTER GLUCURONIC-ACID CONJUGATES WITH THE AID OF OVERSAMPLING AND DIGITAL FILTERING DURING ACQUISITION

Many drugs containing carboxylic acid functional groups are metabolise d in vivo to ester glucuronides (1-O-acyl-beta-D-glucopyranuronates) a nd, of these, a number show a propensity to undergo internal isomerisa tion via a transacylation process, causing the carboxylic acid moiety to migrate successively to the 2-, 3-and 4-positions of the glucuronic acid. These products may be responsible, through reactions with plasm a proteins, for some of the allergenic side effects in a number of non -steroidal anti-inflammatory drugs. It is important to understand thos e properties of the drug molecules which facilitate this reaction, and to this end we have studied the transacylation product formation and reaction kinetics in a series of aryl carboxylic acid glucuronides usi ng NMR spectroscopy. However, the resulting H-1 NMR spectra are very c omplex with much resonance overlap, and recourse to spectral simplific ation processes is necessary. Here, improvement in spectral resolution by oversampling and digital filtering to restrict the detection range of the spectrometer, thus yielding improved digital resolution, is de monstrated. The approach has been applied to the assignment of a mixtu re of transacylated ester glucuronides of 2-trifluoromethylbenzoic aci d through the use of a two-dimensional H-1-H-1 TOCSY experiment.