Characterization of the reaction products of deoxyguanosine with the anticancer agent BFNU and BFNU-1,1,1',1'-d4 in different buffers by high-performance liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.

The products of the reaction of the anticancer agent 1,3-bis(2-fluoroethyl)-1-nitrosourea (BFNU) and BFNU-1,1,1',1'-d4 with the DNA base deoxyguanosine were characterized by applying high-performance liquid chromatography (HPLC)/tandem mass spectrometry. The total effluent from the HPLC column was introduced into the atmospheric pressure ionization (API) source of a triple-quadrupole mass spectrometer via a heated nebulizer. The gasified mixture produced from the heated nebulizer was exposed to corona discharge ionization which led to generation of gas-phase chemical ionization type of ions. The LC/API mass spectrometry produced ions and the tandem mass spectra allowed unambiguous identification, and assignment of positions of the deuterium atoms, in the products of the reaction under a variety of experimental conditions. The identification and characterization of a variety of 7-(2'-haloethyl)guanine derivatives among the reaction products provide confirmation of a proposed mechanism for the action of BFNU on DNA bases.