ISSN:
1052-9306
Schlagwort(e):
Chemistry
;
Analytical Chemistry and Spectroscopy
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
Chlorambucil (p-(di-2-chloroethyl)amino-γ-phenylbutyric acid) is a bifunctional alkylating agent which exhibits acquired drug resistance upon repeated dosing in humans. This compound reacts with glutathione both nonenzymatically and enzymatically in the presence of immobilized microsomal glutathione-S-transferases to produce several glutathione conjugates. These conjugates result from displacement of one or both chlorines by the nucleophilic cysteine sulfhydryl moiety of glutathione. The mono- and diglutathionyl conjugates of chlorambucil were purified by reversed-phase high-performance liquid chromatography and characterized by positive ion fast atom bombardment mass spectrometry. In addition, the mono- and dihydroxy hydrolysis products of chlorambucil were characterized by positive ion thermospray liquid chromatography/mass spectrometry (LC/MS). The glutathione conjugates of chlorambucil did not produce molecular ion species in thermospray LC/MS mode, but gave characteristic ions at m/z 147 corresponding to fragmentation of the glutathione moiety. The formation of glutathione conjugates of this class of alkylating agents may play a role in the development of acquired drug resistance.
Zusätzliches Material:
6 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/bms.1200190408
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