Mass spectrometric (HPLC/ESI--MS/MS) quantification of pyrimido[1,3-a]purin-10(3H)-one, a guanine adduct formed by reaction of malondialdehyde with DNA.
A high performance liquid chromatography/electrospray ionization tandem mass spectrometric (HPLC/ESI MS/MS) method has been developed for quantification of pyrimido[1,2-a]purin-10(3H)-one adducts from DNA. The method is based on acid-catalyzed cleavage of the adducts from DNA and the use of [2,3a,10-13C3]pyrimido[1,2-a]purin-10(3H)-one as an internal standard in the analysis. For this purpose the latter compound was prepared. Rate constants for the acid-catalyzed cleavage of pyrimido[1,2-a]purin-10(3H)-one from the 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.
Hakala
K
K
Department of Chemistry, University of Turku, Finland.
Auriola
S
S
Koivisto
A
A
Lönnberg
H
H
D000143:Acids / Q000494:pharmacology; D000818:Animals; D002384:Catalysis; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics; D008315:Malondialdehyde / Q000737:chemistry / Q000494:pharmacology*; D013058:Mass Spectrometry / Q000379:methods; D011687:Purines / Q000032:analysis* / Q000378:metabolism; D011741:Pyrimidine Nucleosides / Q000378:metabolism; D011743:Pyrimidines / Q000032:analysis* / Q000378:metabolism
D000143:Acids; D018736:DNA Adducts; D011687:Purines; D011741:Pyrimidine Nucleosides; D011743:Pyrimidines; C107643:pyrimido(1,2-a)purin-10(3H)-one; D008315:Malondialdehyde; D004247:DNA