Monitoring of dimethyl sulphate-induced N3-methyladenine, N7-methylguanine and O(6)-methylguanine DNA adducts using reversed-phase high performance liquid chromatography and mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 May 1;867(1):43-8. doi: 10.1016/j.jchromb.2008.03.008. Epub 2008 Mar 14.

Abstract

This work describes the determination of N3-methyladenine, N7-methylguanine and O(6)-methylguanine adducts in dimethyl sulphate-treated salmon-testes DNA employing reversed-phase high performance liquid chromatography (RP-HPLC) with UV-vis detection, followed by mass-spectrometric verification using electrospray ionisation in positive mode ESI(+). Within validation parameters, accuracy, precision, calibration parameters, limit of detection (LOD) and quantitation (LOQ) as well as stability of standard stock solutions were tested and presented for UV/vis detection. The limit of detection (LOD) was found to be 0.1 ng/mL for N3-methyladenine and 0.2 ng/mL for both N7-methylguanine and O(6)-methylguanine (S/N=3). The limit of quantitation (LOQ) was found to be 0.5 ng/mL for all measured compounds, (S/N=10). Quantitative results were obtained for each substance based on eight-point calibration. Intra- and inter-day precisions were within 1.73-6.96 and 2.26-7.58%, respectively, and correlation coefficients of calibration curves (R(2)) ranged from 0.9992 to 0.9997. Relative proportion of N7-methylguanine was accounted for 61.53+/-2.97% (R.S.D.=4.8), N3-methyladenine for 38.19+/-2.99% (R.S.D.=9.6) and O(6)-methylguanine for 0.29+/-0.02% (R.S.D.=5.1), respectively. The application of the above-mentioned techniques provides a valuable contribution for simultaneous determination of methylated DNA adducts, and may represent a suitable approach for similar monitoring/screening studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemistry
  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • DNA / drug effects
  • DNA Adducts / chemistry*
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Male
  • Reference Standards
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization
  • Sulfuric Acid Esters / chemistry
  • Sulfuric Acid Esters / pharmacology*
  • Testis / metabolism

Substances

  • DNA Adducts
  • Sulfuric Acid Esters
  • 3-methyladenine
  • Guanine
  • 7-methylguanine
  • DNA
  • O-(6)-methylguanine
  • Adenine
  • dimethyl sulfate