کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10550943 967097 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evidence of the formation of direct covalent adducts of primaquine, 2-tert-butylprimaquine (NP-96) and monohydroxy metabolite of NP-96 with glutathione and N-acetylcysteine
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Evidence of the formation of direct covalent adducts of primaquine, 2-tert-butylprimaquine (NP-96) and monohydroxy metabolite of NP-96 with glutathione and N-acetylcysteine
چکیده انگلیسی
2-tert-Butylprimaquine (NP-96) is a novel quinoline anti-malarial compound with superior therapeutic profile than primaquine (PQ). Moreover, it is the first 8-aminoquinoline that is established to be devoid of methemoglobin toxicity. The purpose of the present study was to investigate covalent adduct formation tendency of PQ, NP-96 and their phase I metabolites with glutathione (GSH) and N-acetylcysteine (NAc). For the same, the two compounds were incubated in human and rat liver microsomes in the presence of trapping agents and NADPH. In a control set, NADPH was excluded, while a blank was also studied that was devoid of both NADPH and microsomes. The components in the reaction mixtures were initially separated on a C-18 column (250 mm × 4.6 mm, 5 μm) using a mobile phase composed of acetonitrile and 10 mM ammonium acetate in a gradient mode. The samples were then subjected to LC-MSn and LC-HR-MS analyses, and data were collected in full scan MS, data dependent MS/MS, targeted MS/MS, neutral loss scan (NLS) and accurate mass (MS/TOF) modes. In a significant finding, both PQ and NP-96 themselves showed potential to bind covalently with GSH and NAc, as adducts were observed even in the control and blank incubations. Intense peaks corresponding to covalent adduct of mono-hydroxy metabolite of NP-96 with GSH and NAc were also detected in NADPH supplemented reaction solution.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 879, Issue 1, 1 January 2011, Pages 1-7
نویسندگان
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