title: Analysis of urinary aristolactams by on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.
abstract: Aristolochic acids (AAs), nephrotoxicants and known human carcinogens, are a mixture of structurally related derivatives of nitrophenanthrene carboxylic acids with the major components being aristolochic acid I and aristolochic acid II. People may ingest small amounts of AAs from its natural presence in medicinal plants and herbs of the family Aristolochiaceae, including the genera Aristolochia and Asarum, which have been used worldwide in folk medicine for centuries. In order to assess AA intake, an on-line solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry (on-line SPE-LC/MS/MS) method was developed to analyze their most abundant corresponding metabolites, aristolactams (ALs), in urine to serve as biomarkers. The limits of quantitation were 0.006 ng for aristolactam I (AL-I), and 0.024 ng for aristolactam II (AL-II) on column. Recovery varied from 98.0% to 99.5%, and matrix effects were within 75.3-75.4%. This method was applied to analyze ALs in the urine samples collected on days 1, 2, 4, and 7 from mice treated with 30 mg/kg or 50mg/kg AAs. Their half lives were estimated to be 3.55 h and 4.00 for AL-I, and 4.04 and 4.83 h for AL-II, depending on AAs doses. These results demonstrated that the first simple on-line SPE-LC/MS/MS method was successfully developed to analyze urinary ALs with excellent sensitivity and specificity to serve as biomarkers to assess current AA intake from AAs-containing Chinese herbs.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Su-Yin
authors.initials: SY
authors.lastname: Chiang
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Shih
authors.forename: Ho-Tang
authors.initials: HT
authors.lastname: Liao
authors.forename: Po-Chi
authors.initials: PC
authors.lastname: Shu
authors.forename: Ming-Tsai
authors.initials: MT
authors.lastname: Wey
authors.forename: Hei-Feng
authors.initials: HF
authors.lastname: Huang
authors.forename: Kuen-Yuh
authors.initials: KY
authors.lastname: Wu
mesh_terms: D000818:Animals; D034341:Aristolochic Acids / Q000493:pharmacokinetics / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal