Determination of 8-oxo-2′-deoxyguanosine and creatinine in murine and human urine by liquid chromatography/tandem mass spectrometry: application to chemoprevention studies

• Published in: Rapid communications in mass spectrometry 2009-01, Vol.23 (2), p.258-266
• Main Authors: Teichert, Friederike, Verschoyle, Richard D., Greaves, Peter, Thorpe, James F., Mellon, J. Kilian, Steward, William P., Farmer, Peter B., Gescher, Andreas J., Singh, Rajinder
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - urine; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Cell Line, Tumor; Chromatography, High Pressure Liquid - methods; Creatinine - urine; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - urine; Humans; Male; Mice; Mice, Inbred C57BL; Plant Extracts - administration & dosage; Plant Extracts - pharmacokinetics; Prostatic Neoplasms - urine; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods; Tea - chemistry; Urinalysis - methods
• ISSN: 0951-4198; 1097-0231; 1097-0231
• DOI: 10.1002/rcm.3873

Urinary 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐oxodG) represents a non‐invasive biomarker for oxidative stress and may be useful for monitoring chemotherapeutic and chemopreventive interventions associated with cancer‐related alterations in oxidative stress. We describe the development and validation of two separate liquid chromatography/tandem mass spectrometry (LC/MS/MS) selected reaction monitoring (SRM) methods for the determination of 8‐oxodG and creatinine in both murine and human urine using stable isotope labelled internal standards. Levels of 8‐oxodG were normalised to creatinine. The LC/MS/MS methods were applied to two chemoprevention studies utilising tea polyphenols in humans and TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) mice. Patients with benign prostatic hyperplasia received 1 g/day of green tea polyphenols (GTP), 1 g/day of black tea theaflavins (BTT) or no treatment for 4 weeks. TRAMP mice received GTP (0.05% in drinking water) for 4 or 25 weeks. Prostate pathology in TRAMP mice was not affected by GTP. Levels of 8‐oxodG were not altered by tea polyphenols in either mice or humans. In TRAMP mice, urinary 8‐oxodG levels were elevated with increasing age (p