Assignment of the 750 MHz 1H NMR resonances from a mixture of transacylated ester glucuronic acid conjugates with the aid of oversampling and digital filtering during acquisition
| Autor: | R. D. Farrant, Jeremy K. Nicholson, Manfred Spraul, Ian D. Wilson, John C. Lindon, Andrew W. Nicholls |
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| Rok vydání: | 1995 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry Carboxylic acid Clinical Biochemistry Carboxylic Acids Pharmaceutical Science Glucuronates Buffers Xenobiotics Analytical Chemistry chemistry.chemical_compound Transacylation Isomerism Drug Discovery Moiety Spectroscopy chemistry.chemical_classification Electronic Data Processing Aryl Nuclear magnetic resonance spectroscopy Glucuronic acid Combinatorial chemistry Models Chemical chemistry Proton NMR Glucuronide Toluene |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 13:971-977 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/0731-7085(95)01551-u |
| Popis: | Many drugs containing carboxylic acid functional groups are metabolised in vivo to ester glucuronides (1-O-acyl-β- d -glucopyranuronates) and, of these, a number show a propensity to undergo internal isomerisation 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 plasma proteins, for some of the allergenic side effects in a number of non-steroidal anti-inflammatory drugs. It is important to understand those 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 using NMR spectroscopy. However, the resulting 1 H NMR spectra are very complex with much resonance overlap, and recourse to spectral simplification 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 demonstrated. The approach has been applied to the assignment of a mixture of transacylated ester glucuronides of 2-trifluoromethylbenzoic acid through the use of a two-dimensional 1 H- 1 H TOCSY experiment. |
| Databáze: | OpenAIRE |
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