Quantification of the heterocyclic aromatic amine DNA adduct N-(deoxyguanosin-8-yl)-2-amino-3-methylimidazo[4,5-f]quinoline in livers of rats using capillary liquid chromatography/microelectrospray mass spectrometry: a dose-response study

Capillary liquid chromatography/microelectrospray-mass spectrometry (capill ary LC/mu ESI-MS) was used to quantify DNA adducts of the heterocyclic arom atic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in livers of male F ischer-344 rats. Animals received a single oral dose of either 0.05, 0.50, 1.0, or 10 mg/kg IQ and were sacrificed 24 h following treatment. The major lesion identified at all doses was N-(deoxyguanosine-8-yl)-2-amino-3-methy limidazo[4,5-f]quinoline (dG-C8-IQ), The capillary LC/mu ESI-MS method prov ided the means for quantifying 17.5 fmol of dG-C8-IQ (2.0 adducts in 10(8) nucleosides) (S/N 10) in 300 mug of liver DNA with an intra- and interday p recision of 3.5 and 6.6% (RSD), respectively, dG-C8-IQ was quantified with a mean intra-and interday accuracy of 105 +/- 26 and 106 +/- 28 (SD) based on back-calculated adduct masses from five standard curves analyzed over a four-week period. This is the first report on development of a capillary LC /mu ESI-MS method to quantify dG-CS-IQ adducts in liver DNA of rats followi ng dosing with IQ at different levels. Furthermore, the ability to accurate ly and precisely quantify dG-C8-IQ at a level of 2.0 adducts in 108 nucleos ides in vivo makes this method well suited for use in future studies relati ng carcinogen exposure to risk in humans.