Quantification of urinary etheno-DNA adducts by column-switching LC/APCI-MS/MS.
Lipid peroxidation induced etheno-DNA adducts are promutagenic and have been suggested to play a causal role in the development of human cancers. Therefore, human biomonitoring of etheno-DNA adducts in urine has been suggested as a potential marker for oxidative stress-related DNA damage. For quantitative determination, a column-switching LC/APCI-MS/MS method was developed for simultaneous analysis of epsilonAde, epsilondC, and epsilondA in human urine. Quantitative validation parameters (precision, within-day repeatability, and between-day reproducibility) yielded satisfactory results below 10%. Limit of quantification for epsilonAde, epsilondC, and epsilondA was 5.3 fmol, 7.5 fmol, and 1.3 fmol on column, respectively. Mean urinary excretion rates of a six healthy volunteers were 45.8 pmol epsilonAde/24 h, 96.8 pmol epsilondC/24 h, and 18.1 pmol epsilondA/24 h. The demonstrated levels of performance suggest a future applicability of this method to studies of cancer and other diseases related to oxidative stress in humans. To our knowledge, this is the first method described that allows simultaneous determination of epsilonAde, epsilondC, and epsilondA in human urine samples.
Hillestrøm
Peter R
PR
Department of Clinical Pharmacology Q-7642, Rigshospitalet, University Hospital Copenhagen, Tagensvej 20, DK-2200, Copenhagen N, Denmark.
Weimann
Allan
A
Department of Clinical Pharmacology Q-7642, Rigshospitalet, University Hospital Copenhagen, Tagensvej 20, DK-2200, Copenhagen N, Denmark.
Poulsen
Henrik E
HE
Department of Clinical Pharmacology Q-7642, Rigshospitalet, University Hospital Copenhagen, Tagensvej 20, DK-2200, Copenhagen N, Denmark. henrik.enghusen.poulsen@rh.hosp.dk.
D015415:Biomarkers / Q000737:chemistry / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods; D018736:DNA Adducts / Q000737:chemistry / Q000652:urine*; D004249:DNA Damage; D006801:Humans; D015227:Lipid Peroxidation; D013058:Mass Spectrometry / Q000379:methods*; D018384:Oxidative Stress
D015415:Biomarkers; D018736:DNA Adducts