Preparation of N-Ethyl-2'-deoxyguanosine-d as an Internal Standard for the Electrospray Ionization-Tandem Mass Spectrometric Determination of DNA Damage by Acetaldehyde.

The deuteration of N-ethyl-2'-deoxyguanosine (Et-dG), which is a DNA adduct generated from acetaldehyde, was studied by the addition reaction of acetaldehyde-d to 2'-deoxyguanosine (dG) in deuterium oxide (DO), with the aim to obtain an isotope internal standard for the liquid chromatography/tandem mass spectrometry (LC/MS/MS) quantitation of Et-dG. The replacement of the dG C-8 hydrogen atom by a deuteron atom took place at 50°C in DO and afforded a mixture of Et-dG-d and Et-dG-d. Et-dG-d, which was stable in aqueous solutions, was prepared by incubating the mixture in HO at 60°C for 48 h.

Preparation of Cyclic-1,N-propano-2'-deoxyguanosine-d as an Internal Standard for ESI-MS/MS Determination of DNA Damage from Acetaldehyde.

Cyclic-1,N-propano-2'-deoxyguanosine-d (CPr-dG-d) was prepared as an isotopic internal standard (IS) for electrospray ionization tandem mass spectrometry (ESI-MS/MS) quantification of CPr-dG in DNA as a candidate cancer risk marker of acetaldehyde intake, mainly from drinking. The deuterated compound was reasonably synthesized from acetaldehyde-d and 2'-deoxyguanosine in deuterium oxide (DO), preventing the deuterium atoms of acetaldehyde-d from being substituted by hydrogen atoms, which occurred seriously in aqueous synthesis media via keto-enol tautomerism. Furthermore, another deuterium atom was added from DO to form CPr-dG-d.