Mass spectrometric (HPLC/ESI-MS/MS) quantification of pyrimido[1,2-a]purin-10(3H)-one, a guanine adduct formed by reaction of malondialdehyde with DNA

A high performance liquid chromatography/electrospray ionization - tandem m ass spectrometric (HPLC/ESI- MS/ MS) method has been developed for quantifi cation of pyrimido[1,2-a]purin-10(3H)-one adducts from DNA. The method is b ased on acid-catalyzed cleavage of the adducts from DNA and the use of [2,3 a,10-C-13(3)]pyrimido[1,2-a]purin-10(3H)-one as an internal standard in the analysis. For this purpose the latter compound was prepared. Rate constant s for the acidcatalyzed cleavage of pyrimido[1,2-a]purin-10(3H)-one from th e corresponding 2'-deoxyribonucleoside were determined, and its hydrolytic stability and possible formation by a cross reaction between guanine and [2 ,3a,10]pyrimido[1,2-a]purin-10(3H)-one were studied. (C) 1999 Elsevier Scie nce B.V. All rights reserved.