ISSN:
1076-5174
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Physics
Notes:
In a study designed to examine the nature of short-lived, electrophilic intermediates liberated during decomposition of N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU) in vitro and also on administration of BCNU (140 μmol i.p.) to rats in vivo, both on-line and off-line LC/MS/MS techniques were employed to detect and characterize the corresponding glutathione (GSH) adducts present in incubation media and excreted into bile, respectively. In vitro, four GSH conjugates were formed and these were identified, on the basis of their product ion spectra, as products of S-and N-carbamoylation and alkylation reactions. Although the relative proportions of these in vitro adducts were found to depend on the molar ratios of GSH and BCNU, the major adduct under all conditions studied proved to be S-(2-chloroethylcarbamoyl)glutathione (SCG). Analysis of untreated bile samples by means of on-line LC/MS/MS with constant neutral loss (129 u) and precursor ion (m/z 179) scanning techniques again led to the detection of four GSH conjugates, although only one of these (SCG) was common to the group of adducts identified in vitro. All of the GSH conjugates detected in bile represented products of S-carbamoylation, indicating that the alkylating moiety released from BCNU undergoes reactions in vivo with nucleophiles other than GSH.
Additional Material:
10 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jms.1190300111
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