Determination of in vitro formed DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine using capillary liquid chromatography/electrospray ionization/tandem mass spectrometry.
On-line reversed-phase capillary liquid chromatography/tandem mass spectrometry with electrospray ionization was used for the detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) adducts of DNA and compared to analysis by 32P-postlabeling. Structural information was obtained on low nanogram levels of a synthetic N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) standard using collision-induced dissociation, and low picogram level detection was achieved for the targeted dG-C8-PhIP adduct using the selective multiple reaction monitoring scanning mode. The method was applied to the analysis of an in vitro reaction mixture identifying the dG-C8-PhIP adduct and providing evidence for the presence of two additional PhIP-modified deoxyguanosine adducts. The results were in qualitative agreement with those obtained by the 32P-postlabeling method. In addition, the mass spectrometric results revealed the occurrence of an unexpected product in the in vitro reaction mixture presumably resulting from cleavage through the guanine base.
Rindgen
D
D
Barnett Institute, Northeastern University, Boston, Massachusetts 02115, USA.
Turesky
R J
RJ
Vouros
P
P
D002853:Chromatography, Liquid; D018736:DNA Adducts / Q000032:analysis*; D007093:Imidazoles / Q000378:metabolism*; D013058:Mass Spectrometry; D009153:Mutagens / Q000378:metabolism*
D018736:DNA Adducts; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine