Graduate Thesis Or Dissertation
 

Analytical chemistry of pentazocine metabolites produced by the greyhound

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/mp48sh74c

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  • This thesis concerns itself mainly with analytical methods development and analytical applications in the field of drug metabolism studies. The determination of the analgesic pentazocine and its metabolites in the greyhound are studied. Pentazocine and all of its possible metabolites are isolated from the greyhound urine by a the multi-solvent extraction and XAD-2 column after enzymatic hydrolysis. The optimization of subsequently applied chromatographic separation techniques are studied, and a useful strategy for the separation of analgesics like pentazocine and its metabolites is devised. As a result, nine pentazocine metabolites were recovered from the greyhound urine and metabolic isomers were successfully separated by the HPLC assay developed. Mass spectroscopic fragmentations of trimethylsilylated pentazocine upon electron impact (EI) are described. The identification of positional isomers due to different functional group attachment to the end of the side chain is achieved by the fragmentations proposed. The EI mass spectra of nine pentazocine metabolites including three pairs of new metabolic isomers are interpreted based on the fact that the biotransformation of a drug results in structurally similar metabolites. A complete NMR assignment of pentazocine is conducted emphasizing the choice and utilization of selected 1D and 2D NMR methods to determine the molecular structure and conformation of a complex organic molecule. An NMR analysis protocol is proposed whereby a pentazocine metabolite can be characterized without a synthetic reference. A newly discovered pentazocine metabolite is identified as 8-methoxyl pentazocine by using the NMR analysis strategies devised. These results show three pairs of new metabolic isomers of pentazocine in greyhound urine. Three of the new isomers have a methoxyl group attached to the aromatic ring at the 8-position and a hydroxyl group at the 9-position. Their isomers are formed by interchanging these two groups between these two sites. It is concluded that, in addition to oxidative metabolism on the side chain observed in most other species, pentazocine has also undergone the hydroxylation and methylation of the aromatic ring in the greyhound metabolism.
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