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

Capillary liquid chromatography-continuous-flow fast atom bombardment mass spectrometry is applied to the detection of deoxynucleoside adduc ts of N-acetoxy-N-acetyl-2-aminofluorene. In such a configuration, nor mal 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) amoun ts sampled. In addition, multiple reaction monitoring gives limits of detection below 25 pg (50 fmol) for this adduct, suggesting the potent ial for routine screening of intact deoxynucleoside adducts formed bel ow the 1:10(6) level from as little as 1 mg of DNA. When applied to th e 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 N-2 and C8 deoxyguan osine adducts formed.