Document Detail

Determination of free and glucuronated hexane metabolites without prior hydrolysis by liquid- and gas-chromatography coupled with mass spectrometry.
MedLine Citation:
PMID:  10511266     Owner:  NLM     Status:  MEDLINE    
Since n-hexane metabolites are excreted as glucuronide conjugates, most conventional analytical procedures require preliminary hydrolysis, yielding to the 'total' 2,5-hexanedione (2,5-HD), but also giving rise to a number of artifacts. The whole pattern of n-hexane metabolites, both conjugated and unconjugated, as well as different methods of sample pretreatment have been evaluated by hyphenated techniques (liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS)). Aliquots of urine from rats exposed to n-hexane underwent enzymatic or acid hydrolysis or both; whereas one aliquot was applied to LC-MS, dichloromethane extracts were analyzed by GC-MS. In untreated urine, four glucuronides (-G) were identified and characterized by LC-MS: 2-hexanol-G, 5-hydroxy-2-hexanone-G, 4,5-dyhydroxy-2-hexanone-G, and 2,5-hexanediol-G. 'Free' 2,5-HD was detectable in non-hydrolyzed samples by both GC- and LC-MS. Whereas enzymatic hydrolysis did not increase the amount of 2,5-HD, acid hydrolysis led to increase 2,5-HD in variable amount and produced gamma-valerolactone as a result of a complete transformation of 4,5-dihydroxy-2-hexanone-G and the partial conversion from 5-hydroxy-2-hexanone-G. Further experiments showed that both 5-hydroxy-2-hexanone-G and 4,5-dihydroxy-2-hexanone-G, isolated by solid-phase extraction and hydrolyzed, yield comparable amount of 2,5-HD and gamma-valerolactone. In samples treated by acid hydrolysis, GC-MS only does not allow to understand the true source of 'total' 2,5-HD, which may be produced not only from 4,5-dihydroxy-2-hexanone-G but also from the more abundant 5-hydroxy-2-hexanone-G, which thus represents the main source of analytical artifacts. 'Free' 2,5-HD seems to be both suitable from an analytical point of view and meaningful for biological monitoring purposes, provided that conjugate metabolites are rapidly removed from the body leading to a negligible neurotoxic risk.
P Manini; R Andreoli; A Mutti; E Bergamaschi; I Franchini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology letters     Volume:  108     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-10-20     Completed Date:  1999-10-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  225-31     Citation Subset:  IM    
Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma Medical School, Italy.
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MeSH Terms
Chromatography, Gas / methods
Chromatography, Liquid / methods
Gas Chromatography-Mass Spectrometry / methods
Glucuronates / urine*
Hexanes / metabolism*,  toxicity,  urine
Hexanols / urine
Hexanones / urine
Rats, Sprague-Dawley
Reg. No./Substance:
0/Acids; 0/Enzymes; 0/Glucuronates; 0/Hexanes; 0/Hexanols; 0/Hexanones; 110-13-4/2,5-hexanedione; 110-54-3/n-hexane; 111-27-3/1-hexanol; 113201-38-0/4,5-dihydroxy-2-hexanone; 626-93-7/2-hexanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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