Detection of in vivo formed DNA adducts at the part-per-billion level 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-amino-3-methylimidazo[4,5-f]quinoline (IQ) from in vivo sources. Adjustments were made to a previously described methodology such that analyte detection could be improved by nearly 2 orders of magnitude. These adjustments included changing the electrospray ionization sprayer configuration, increasing the sample injection volume, improving the solid-phase extraction procedure, and increasing peak efficiency by modifying chromatographic conditions. while this scheme for improving analyte detection was targeted for DNA adducts, it could be applied to almost any LC/MS methodology where sensitive analysis is the primary objective. Selective reaction monitoring) techniques with a triple quadrupole mass spectrometer enabled sensitive and specific detection of IQ adducts, with detection limits approaching 1 adduct in 10(9) unmodified bases using similar to 500 mug of DNA. The DNA adducts N-(2 ' -deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline and 5-(2 ' -deoxyguanosin-N-2-yl)-2-amino-3 -methylimidazo[4,5-f]quinoline were detected in pancreas tissue of a cynomolgus monkey sacrificed 24 h after a single administration of 10 mg/kg carcinogen. The LC/MS results were consistent with previously published P-32-postlabeling data (Turesky et al. Chem Res. Toxicol. 1996, 9, 403-408). Thus, capillary tandem LC/MS is a highly sensitive technique, which can be used to screen for DNA adducts in vivo.