Simultaneous quantification of three alkylated‑purine adducts in human urine using sulfonic acid poly(glycidyl methacrylate‑divinylbenzene)-based microspheres as sorbent combined with LC-MS/MS

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 1:1081-1082:15-24. doi: 10.1016/j.jchromb.2018.02.028.

Abstract

Three alkylated DNA adducts, N3‑methyladenine, N3‑ethyladenine and N7‑ethylguanine, have been proved to be potential biomarkers for DNA injury caused by exposure to cigarette smoke. In this study, a highly specific and sensitive method using a new mixed-mode sulfonate-functionalized poly(glycidyl methacrylate-divinylbenzene) as a solid-phase extraction sorbent was developed for the analysis of these three alkylated-purine adducts in human urine. Under optimized conditions, the prepared sorbent interacts strongly with these urinary adducts, demonstrating high clean-up efficiency and extraction recovery. The method detection limits (S/N ≥ 3) of N3-MeA, N3-EtA and N7-EtG were 1.75, 0.20, and 0.15 pg mL-1, respectively, while the method quantitation limits were found to be 5.78, 0.66, and 0.49 pg mL-1 for N3-MeA, N3-EtA and N7-EtG, respectively. The intra-day and inter-day precisions were investigated, of which were in the range of 1.6-3.8% and 3.2-5.6%, respectively. The recovery values of the alkylated DNA adducts in spiked urine sample were ranged 89.7-104.5%. Their concentrations were statistically significantly higher in smokers than in nonsmokers. These results show that the proposed method is suitable for the analysis of alkylated DNA adducts.

Keywords: Alkylated-purine adducts; Human urine; LC-MS/MS; Poly(glycidyl methacrylate‑divinylbenzene)-based microspheres; Solid phase extraction.

MeSH terms

  • Adult
  • Alkylation
  • Biomarkers
  • Chromatography, Liquid / methods*
  • DNA Adducts / chemistry
  • DNA Adducts / isolation & purification
  • DNA Adducts / urine*
  • Epoxy Compounds / chemistry
  • Humans
  • Linear Models
  • Male
  • Methacrylates / chemistry
  • Microspheres*
  • Purines / chemistry
  • Purines / isolation & purification
  • Purines / urine*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Smoking
  • Solid Phase Extraction / methods
  • Sulfonic Acids / chemistry
  • Tandem Mass Spectrometry / methods*
  • Vinyl Compounds / chemistry
  • Young Adult

Substances

  • Biomarkers
  • DNA Adducts
  • Epoxy Compounds
  • Methacrylates
  • Purines
  • Sulfonic Acids
  • Vinyl Compounds
  • divinyl benzene
  • glycidyl methacrylate