Subpicogram per Milliliter Determination of the Tobacco-Specific Carcinogen Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Human Urine Using Liquid Chromatography-Tandem Mass Spectrometry
Subpicogram per Milliliter Determination of the Tobacco-Specific Carcinogen Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Human Urine Using Liquid Chromatography-Tandem Mass Spectrometry
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DOI：
10.1021/ac8009005
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发表时间：
2008-11-01
影响因子：
7.4
通讯作者：
Benowitz, Neal L.
中科院分区：
文献类型：
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作者：
Jacob, Peyton, III;Havel, Christopher;Benowitz, Neal L.
接触二手烟草烟雾（SHS）与包括肺癌在内的许多疾病的风险增加有关。烟草特异性亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）由于其在动物中产生肺肿瘤的效力和特异性而特别令人感兴趣。尿液中的NNK代谢物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）经常用作暴露的生物标志物。由于其半衰期长（40-45天），NNAL可提供长期、时间平均的接触测量。建立了一种高灵敏度的液相色谱-串联质谱法测定人尿中NNAL的方法。该方法包括液-液萃取，然后转化为己酸酯衍生物。这种衍生物有助于通过提取和色谱法从干扰尿液成分中分离，并增强电喷雾电离质谱法的检测。对于5 mL尿液标本，定量下限为0.25 pg/mL。应用程序的人与一系列不同的SHS暴露水平的研究。
Exposure to secondhand tobacco smoke (SHS) has been linked to increased risk for a number of diseases, including lung cancer. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is of particular interest due to its potency and its specificity in producing lung tumors in animals. The NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine is frequently used as a biomarker for exposure. Due to its long half-life (40-45 days), NNAL may provide a long-term, time-averaged measure of exposure. We developed a highly sensitive liquid chromatography-tandem mass spectrometry method for determination of NNAL in human urine. The method involves liquid-liquid extraction followed by conversion to the hexanoate ester derivative. This derivative facilitates separation from interfering urinary constituents by extraction and chromatography and enhances detection with electrospray ionization mass spectrometry. The lower limit of quantitation is 0.25 pg/mL for 5-mL urine specimens. Applications to studies of people with a range of different SHS exposure levels is described.