Determination of in Vitro- and in Vivo-Formed DNA Adducts of 2-Amino-3-methylimidazo[4,5-f]quinoline by Capillary Liquid Chromatography/Microelectrospray Mass Spectrometry

Capillary liquid chromatography/microelectrospray mass spectrometry has been applied to the detection of deoxyribonucleoside adducts of the food-derived mutagen 2-ammo-3-methylimidazo[4,5-f]quinoline (IQ) from in vitro and in vivo sources. Constant neutral loss (CNL) and selective reaction monitoring (SRM) techniques with a triple-quadrupole mass spectrometer enabled sensitive and specific detection of IQ adducts in vitro and in animals. Detection of I adduct in 10^4 unmodified bases is achieved using CNL scanning detection, while the lower detection limits using SRM approach I adduct in 10^7 unmodified bases using 300 mug of DNA. The DNA adducts N-(deoxyguanosin-8-yl)-2-ammo-3-methylimidazo[4,5-f]quinoline (dG-C8IQ) and 5-(deoxyguanosin-N^2-yl)-2-amino-3-methylimidazo[4,5-f]quinolme (dG-A^-IQ) were detected in kidney tissues of chronically treated cynomolgus monkeys at levels and in proportions consistent with previously published 32P-postlabeling data [Turesky, R. J., et al. (1996) Chem. Res. Toxicol. 9, 403-408]. Thus, capillary tandem LC/MS is a highly sensitive technique, which can be used to screen for DNA adducts in vivo.