Implementation of data-dependent acquisitions in the study of melphalan DNA adducts by miniaturized liquid chromatography coupled to electrospray tandem mass spectrometry.
The study of defects in DNA caused by xenobiotics, more particularly the study of DNA adducts, is an important field in cancer aetiology. The analysis of low abundance DNA adducts formed in vivo both in animals and humans requires the development and implementation of highly sensitive analytical methods. Since only a minute amount of DNA can be isolated (ca. 100 microg) it is evident that the amount of sample consumed per analysis should be as small as possible in order to gather as much analytical information as possible. In this article an example is given of how this problem can be solved by the implementation of data-dependent acquisitions using capillary liquid chromatography coupled to electrospray tandem mass spectrometry. As a case study the alkylation of DNA by melphalan is presented. Slight modifications of the chromatographic conditions (mobile and stationary phases) can allow the automated analysis of other kinds of DNA adducts.
Department of Chemistry, Nucleoside Research and Mass Spectrometry Unit, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Bart
B
Van den Driessche
Walter
W
Van Dongen
Filip
F
Lemière
Eddy L
EL
Esmans
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor / Q000737:chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry*; D006801:Humans; D019169:Jurkat Cells; D008558:Melphalan / Q000737:chemistry* / Q000494:pharmacology; D008832:Microchemistry / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
D018906:Antineoplastic Agents, Alkylating; D018736:DNA Adducts; D004247:DNA; D008558:Melphalan