Preparation of Cyclic-1,N2-propano-2'-deoxyguanosine-d7 as an Internal Standard for ESI-MS/MS Determination of DNA Damage from Acetaldehyde

Anal Sci. 2019 Dec 10;35(12):1393-1397. doi: 10.2116/analsci.19N023. Epub 2019 Aug 30.

Abstract

Cyclic-1,N2-propano-2'-deoxyguanosine-d7 (CPr-dG-d7) 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-d4 and 2'-deoxyguanosine in deuterium oxide (D2O), preventing the deuterium atoms of acetaldehyde-d4 from being substituted by hydrogen atoms, which occurred seriously in aqueous synthesis media via keto-enol tautomerism. Furthermore, another deuterium atom was added from D2O to form CPr-dG-d7. After four weeks of storage in H2O at 10°C, CPr-dG-d7 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-d7 as the IS showed sufficient linearity from 1.0 × 10-10 to 4.0 × 10-9 M with r2 = 0.998.

Keywords: Cyclic-1,N2-propano-2′-deoxyguanosine-d7; D2O; ESI-MS/MS; acetaldehyde-d4; cancer risk marker; isotopic internal standard.

MeSH terms

  • Acetaldehyde / toxicity*
  • Calibration
  • DNA Damage*
  • Deoxyguanosine / chemistry*
  • Mutagens / toxicity*
  • Reference Standards
  • Spectrometry, Mass, Electrospray Ionization / standards*
  • Tandem Mass Spectrometry / standards*

Substances

  • Mutagens
  • Deoxyguanosine
  • Acetaldehyde