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Analysis of oxycodol and noroxycodol stereoisomers in biological samples by capillary electrophoresis
Author(s) -
Baldacci Andrea,
Thormann Wolfgang
Publication year - 2005
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200410301
Subject(s) - chemistry , diastereomer , chromatography , capillary electrophoresis , cyclodextrin , stereoselectivity , hydrolysis , in vivo , beta cyclodextrins , beta (programming language) , enantiomer , stereoisomerism , in vitro , stereochemistry , organic chemistry , biochemistry , molecule , microbiology and biotechnology , biology , catalysis , computer science , programming language
Abstract A capillary electrophoresis (CE) method for the separation of the diastereoisomers of 6‐oxycodol (6OCOL) and nor‐6‐oxycodol (N6OCOL), the 6‐keto‐reduced metabolites of oxycodone (OCOD) and noroxycodone (NOCOD), respectively, is reported and employed to assess the stereoselectivity of these metabolic steps in vivo , in vitro , and in chemical synthesis. CE in an untreated fused‐silica capillary with acidic buffers containing 2‐hydroxypropyl‐β‐cyclodextrin, randomly sulfated β‐cyclodextrin, or single isomer heptakis(2,3‐diacetyl‐6‐sulfato)‐β‐cyclodextrin (HDAS‐β‐CD) is shown to permit the simultaneous separation of the stereoisomers of 6OCOL and N6OCOL. A 100 m M phosphate buffer of pH 2.0 containing 2.05% w/v HDAS‐β‐CD provides a medium for rapid analysis and unambiguous identification of these stereoisomers in solid‐phase extracts of (i) urines stemming from patients under pharmacotherapy with OCOD, (ii) incubations of OCOD and NOCOD with human liver cytosol and the human liver S9 fraction, and (iii) after chemical synthesis from OCOD and NOCOD using NaBH 4 . In all cases, α‐N6OCOL is shown to be the predominant stereoisomer of N6OCOL. For 6OCOL, the same is true for in vitro formation and for chemical synthesis. In urine, however, β‐6OCOL is observed to be excreted in a higher amount than α‐6OCOL. For the urinary α‐/β‐isomer ratio of 6OCOL and N6OCOL, there are no differences between the data obtained for nonhydrolyzed and enzymatically hydrolyzed urines. The data document the stereoselectivity of the 6‐keto‐reduction of OCOD and NOCOD in man.