title: [Biomonitoring method of dermal exposure to sulfur mustard based on DNA adduct in lung of SD rats by high performance liquid chromatography-electrospray ionization tandem mass spectrometry].
abstract: The analysis of biological samples can provide qualitative and quantitative evidence of exposure to sulfur mustard (SM). N7-(2-hydroxyethylthioethyl) guanine (N7-HETEG) is the most abundant DNA adduct and one of the biomarkers of SM exposure. For the detection and validation of SM exposure, a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of N7-HETEG in a biomedical sample was developed, using N7-benzylguanine as the internal standard. The method was validated and showed the limit of detection of 300 pg/mL (S/N > or =10) and limit of quantitation of 850 pg/mL (S/N > or =20). The linear range was 300 pg/mL-1.28 microg/mL, with both the values of intraday and interday relative standard deviations of less than 10% (n =7) over the calibration range. The recoveries varied from 100% to 132%. The method was applied for the determination of N7-HETEG in the lung of SD rats caused by dermal exposure to SM in vivo. Under the exposure to SM of 5.5, 11, 22 and 45 mg/kg, respectively, (0.56 +/- 0.16), (0.67 +/- 0.12), (1.36 +/- 0.68) and (5.14 +/- 0.92) ng of N7-HETEG per gram of SD rat lung tissue were found after four days of exposure. The amount of N7-HETEG increased with the exposed doses, and it can act as a biomarker of sulfur mustard exposure.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 10085, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yue
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wei
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Nini
authors.initials: N
authors.lastname: Lin
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Yajiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018736:DNA Adducts / Q000187:drug effects*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D018736:DNA Adducts; D009151:Mustard Gas