Application of capillary liquid chromatography coupled with tandem mass spectrometric methods to the rapid screening of adducts formed by the reaction of N-acetoxy-N-acetyl-2-aminofluorene with calf thymus DNA.

Abstract

Capillary liquid chromatography-continuous-flow fast atom bombardment mass spectrometry is applied to the detection of deoxynucleoside adducts of N-acetoxy-N-acetyl-2-aminofluorene. In such a configuration, normal scan and tandem mass spectrometric techniques are shown to provide useful structural information for an N-acetyl-N-(deoxyguanosin-8-yl)-2-aminofluorene adduct standard for low- nanogram (low-picomole) amounts sampled. In addition, multiple reaction monitoring gives limits of detection below 25 pg (50 fmol) for this adduct, suggesting the potential for routine screening of intact deoxynucleoside adducts formed below the 1:10(6) level from as little as 1 mg of DNA. When applied to the analysis of the products of an in vitro reaction of calf thymus DNA with N-acetoxy-N-acetyl-2-aminofluorene, these techniques are readily able to detect and supply structural data for the N2 and C8 deoxyguanosine adducts formed.