کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7617685 1494082 2014 30 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Simultaneous determination of four sulfur mustard-DNA adducts in rabbit urine after dermal exposure by isotope-dilution liquid chromatography-tandem mass spectrometry
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Simultaneous determination of four sulfur mustard-DNA adducts in rabbit urine after dermal exposure by isotope-dilution liquid chromatography-tandem mass spectrometry
چکیده انگلیسی
Sulfur mustard (SM) is a classic vesicant agent, which has been greatly employed in several wars or military conflicts. The most lesion mechanism is its strong alkylation of DNAs in vivo. Until now there are four specific DNA adducts of SM identified for further retrospective detection, i.e., N7-(2-hydroxyethylthioethyl)-2′-guanine (N7-HETEG), bis(2-ethyl-N7-guanine)thioether (Bis-G), N3-(2-hydroxyethylthioethyl)-2′-adenine (N3-HETEA) and O6-(2-hydroxyethylthioethyl)-2′-guanine (O6-HETEG), respectively. Here, a novel and sensitive method of isotope-dilution ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combining with solid phase extraction was reported for the simultaneous determination of four SM-DNA adducts. A lower limit of detection of 2-5 ng L−1, and a lower limit of quantitation of 5-10 ng L−1 were achieved, respectively, and the recoveries ranged from 87% to 116%. We applied this method in the determination of four SM-DNA adducts in rabbit urine after dermal exposure by SM in three dose levels (2, 5, 15 mg kg−1), so as to investigate the related metabolic behavior in vivo. For the first time, in SM exposed rabbit urine, our results revealed the relative accumulation abundance of four SM-DNA adducts, i.e., 67.4% for N7-HETEG, 22.7% for Bis-G, 9.8% for N3-HETEA, 0.1% for O6-HETEG, and significant dose and time dependent responses of these SM-DNA adducts. The four adducts were detectable after 8 h, afterwards, their contents continuously increased, achieved maximum in the first two or three days and then gradually decreased till the end of one month. Meanwhile, the amounts of SM-DNA adducts were positively correlated with the exposure doses.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 961, 15 June 2014, Pages 29-35
نویسندگان
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