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. After four weeks of storage in HO at 10°C, CPr-dG-d was found to be sufficiently stable for practical use. The calibration curve of CPr-dG by using a hydrophilic interaction chromatography-ESI-MS/MS system with CPr-dG-d as the IS showed sufficient linearity from 1.0 × 10 to 4.0 × 10 M with r = 0.998.