Abstract
A sensitive high-performance liquid chromatography method with fluorescence detection (HPLC-FLD) for the determination of DNA adducts induced by nephrotoxic and carcinogenic aristolochic acid (AA) is presented. The DNA adduct of AAII (dA-AAII) was synthesized by in vitro incubation, purified by preparative HPLC, characterized using fluorescence spectroscopy and high-resolution mass spectrometry, and was used as the biomarker for AA exposure in rats. The developed HPLC-FLD method was validated and applied for the determination of dA-AAII in rat kidney tissues. The method provided a detection limit of 18.3 fmol, which allowed the detection of dA-AAII in the rat kidney tissue samples collected after a single oral dose of AA. dA-AAII was detected in the kidney DNA digestion extracts of the rats that were dosed with AA at 5 mg/kg and 30 mg/kg at concentrations of 6.2 ± 1.1 and 41.3 ± 8.0 dA-AAII per 109 normal dA, respectively.
Original language | English |
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Pages (from-to) | 848-852 |
Number of pages | 5 |
Journal | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
Volume | 877 |
Issue number | 10 |
DOIs | |
Publication status | Published - 1 Apr 2009 |
User-Defined Keywords
- Aristolochic acid
- DNA-AA adduct
- Fluorescence detection
- High-performance liquid chromatography
- Kidney tissue