ISSN:
0951-4198
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Physics
Notes:
The reaction pathway of alkylating agents is often exploited in the design of bifunctional anti-cancer drugs. These drugs form mono-DNA adducts as well as inter- and intra-strand cross-linked adducts, notably by reaction at DNA bases, including the N-7-position of guanine (G). A positive-ion fast-atom bombardment (FAB) mass spectrum of an in vitro preparation of DNA alkylated with phosphoramide mustard (the active metabolite of the anti-cancer drug cyclophosphamide) indicated the presence of the two mono-DNA adducts N-(2-chloroethyl)-N-[2-(7-guaninyl)ethyl] amine, designated NOR—G, and N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl] amine, designated NOR—G—OH, (MH+ 257/259 and 239, respectively) but not the presence of the cross-linked adduct N,N-bis-[2-(7-guaninyl)ethyl] amine, designated G—NOR—G (MH+ 372). Using synthetic standards, daughterion spectra of NOR—G, NOR—G—OH and G—NOR—G were obtained (matrix 0.2 M p-toluene sulphonic acid in glycerol) by positive-ion FAB tandem mass spectrometry (FAB-MS/MS). The daughter-ion spectra of both mono-DNA adducts NOR—G and NOR—G—OH contained a fragment ion at m/z 152 [G + H]+, whereas the cross-linked adduct, G—NOR—G, showed an ion at m/z221, [MH - G]+. Evidence for the presence of NOR—G, NOR—G—OH and G—NOR—G in the in vitro preparation was obtained by performing a double parent-ion scan on m/z 152 and 221. The presence of G—NOR—G was further supported by performing a single parent-ion scan on m/z 221. The use of this MS/MS technique should eliminate the need for intricate sample purification in the identification of G—NOR—G in biological extracts.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/rcm.1290041014
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