Study of the metabolism on tobacco-specific N-nitrosamines in the rabbit by solid-phase extraction and liquid chromatography-tandem mass spectrometry
Study of the metabolism on tobacco-specific N-nitrosamines in the rabbit by solid-phase extraction and liquid chromatography-tandem mass spectrometry
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固相萃取-液相色谱-串联质谱法研究烟草特有的N-亚硝胺在兔体内的代谢
DOI：
10.1007/s00216-006-0884-5
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发表时间：
2006-12-01
影响因子：
4.3
通讯作者：
Liu, Huwei
中科院分区：
文献类型：
--
作者：
Li, Chenchen;Wen, Dawei;Liu, Huwei
采用固相萃取和LC-MS-MS联用技术研究了烟草特有的N-亚硝胺、N‘-亚硝基烟碱、N’-亚硝基烟碱、N‘-亚硝基烟碱和4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone在烟草中的代谢。以4-(甲基亚硝氨基)-4-(3-吡啶)-1-丁醇(iso-NNAL)为内标。固相萃取和LC-MS-MS是一种快速、简便、灵敏、选择性好的分析兔血清中TSNAs的方法。5 ng mL(-1)和0.5ngmL(-1)标准品的相对标准偏差(RSD，n=6)为2.1%~11%，血清中5 ng mL(-1)标准品的加标回收率为100.2%~112.9%。NNAL和其他4种TSNAs的峰面积比与浓度在0.2~100ngmL(-1)和0.5~100ngmL(-1)范围内呈良好的线性关系，相关系数(R-2)为0.99(线性回归和对数回归)。标准物质在溶剂中的检出限为0.04~0.10ngmL(-1)。根据香烟中TSNAs含量的不同，兔耳静脉注射TSNAs的剂量分别为4.67mgkg(-1)和11.67mgkg(-1)。得到了4种TSNAs和NNK的代谢物4-(甲基亚硝基)-1-(3-吡啶)-1-丁醇(NNAL)的代谢曲线，并在此基础上通过非线性曲线拟合建立了这些TSNAs的代谢动力学方程。
Metabolism of four tobacco-specific N-nitrosamines (TSNAs), N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N'-nitrosoanabasine (NAB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been studied by solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS-MS). 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was used as internal standard. SPE and LC-MS-MS was found to be a rapid, simple, sensitive, and selective method for analysis of TSNAs in rabbit serum. The relative standard deviation (R.S.D., n = 6) for analysis of 5 ng mL(-1) and 0.5 ng mL(-1) standards and of serum sample spiked with 5 ng mL(-1)standards of five TSNAs was 2.1-11% and recovery of 5 ng mL(-1) standards from serum was 100.2-112.9%. A good linear relationship was obtained between peak area ratio and concentration in the range of 0.2-100 ng mL(-1) for NNAL and 0.5-100 ng mL(-1) for other four TSNAs, with correlation coefficients (R-2)> 0.99 (both linear and log-log regression). Detection limits for standards in solvent were between 0.04 and 0.10 ng mL(-1). Doses of TSNAs administered to rabbits via the auricular vein were 4.67 mu g kg(-1) and 11.67 mu g kg(-1), in accordance with the different levels in cigarettes. Metabolic curves were obtained for the four TSNAs and for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of NNK; on the basis of these curves we modeled metabolic kinetic equations for these TSNAs by nonlinear curve fitting.