Nicotine exposure and metabolizer phenotypes from analysis of urinary nicotine and its 15 metabolites by LC-MS.
Nicotine exposure and metabolizer phenotypes from analysis of urinary nicotine and its 15 metabolites by LC-MS.
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DOI：
10.4155/bio.11.42
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发表时间：
2011-04
期刊：
影响因子：
1.8
通讯作者：
Blair IA
中科院分区：
文献类型：
--
作者：
Rangiah K;Hwang WT;Mesaros C;Vachani A;Blair IA
吸得不深的吸烟者接触到的烟草烟雾中的有毒物质较少。为了更严格地评估烟草烟雾暴露，有必要有一种准确的方法来量化尼古丁及其所有已知的代谢物。建立了一种稳定同位素稀释LC-MRM /MS分析方法，用于定量尿尼古丁和15种可能来自已知代谢途径的代谢物。直接法测定烟碱、可替宁、反式-3′-羟基可替宁、烟碱- n -氧化物、可替宁- n -氧化物、去甲烟碱、去甲可替宁和4-羟基-4-（3-吡啶基）丁酸。用β-葡萄糖醛酸酶水解尿液，定量测定相应的葡萄糖醛酸代谢产物。采用LC - MRM/MS对61例吸烟者尿液中的尼古丁及15种尼古丁代谢物进行了定量分析。尿中尼古丁和代谢物浓度变化范围为7.9 ~ 337.8 μM（平均75.5±67.8 μM）。建立了三种尼古丁代谢物表型，分别为减少型代谢物（比值< 8）、正常型代谢物（比值8 - 30）和广泛型代谢物（比值bbb30）。4-羟基-4-（3-吡啶基）丁酸在所有三种表型中都是丰富的代谢物，此前尚未被量化。使用这种检测方法，现在可以确定尼古丁暴露和/或代谢物表型与暴露于烟草烟雾中存在的有毒物质和/或与吸烟的生物反应生物标志物之间是否存在关系。这将有助于识别患吸烟相关疾病的高风险人群以及适合戒烟计划的人群。
Smokers who inhale less deeply are exposed to lower amounts of the toxic substances present in tobacco smoke. In order to more rigorously assess tobacco smoke exposure, it is necessary to have an accurate method for quantifying nicotine and all of its known metabolites. A stable-isotope dilution LC–MRM/MS assay has been developed for quantification of urinary nicotine and the 15 possible metabolites that could arise from known metabolic pathways. Nicotine, cotinine, trans-3′-hydroxy-cotinine, nicotine-N-oxide, cotinine-N-oxide, nornicotine, norcotinine and 4-hydroxy-4-(3-pyridyl)butanoic acid were quantified by direct analysis. The corresponding glucuronide metabolites were quantified after urine hydrolysis with β-glucuronidase. Nicotine and all 15 nicotine metabolites were quantified by LC MRM/MS in most urine samples from 61 tobacco smokers. Urinary nicotine and metabolite concentrations ranged from 7.9 to 337.8 μM (mean 75.5 ± 67.8 μM). Three nicotine metabolizer phenotypes were established as reduced metabolizers (ratio < 8), normal metabolizers (ratio 8–30), and extensive metabolizers (ratio > 30). 4-hydroxy-4-(3-pyridyl)butanoic acid, which has not been quantified previously, was an abundant metabolite in all three phenotypes. Using this assay it will now be possible to determine whether there are relationships between nicotine exposure and/or metabolizer phenotype with exposure to toxic substances that are present in tobacco smoke and/or to biological response biomarkers to tobacco smoking. This will help in identifying individuals at high risk for developing smoking-related diseases as well as those amenable to smoking cessation programs.
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DOI：
10.1124/jpet.109.159855
发表时间：
2010-01-01
影响因子：
3.5
作者：
Berg, Jeannette Zinggeler;Mason, Jesse;Murphy, Sharon E.
通讯作者：
Murphy, Sharon E.
影响因子：
3.9
作者：
Bao, ZP;He, XY;Hong, JY
通讯作者：
Hong, JY
DOI：
10.1073/pnas.220207697
发表时间：
2000-11-07
影响因子：
11.1
作者：
Hecht, SS;Hochalter, JB;Murphy, SE
通讯作者：
Murphy, SE
影响因子：
1.8
作者：
Heavner, DL;Richardson, JD;Ogden, MW
通讯作者：
Ogden, MW
DOI：
10.1007/bf03189632
发表时间：
1982-01-01
影响因子：
1.9
作者：
GORROD, JW;HIBBERD, AR
通讯作者：
HIBBERD, AR