中文摘要：

为准确测定小鼠血液中4-（N-甲基-N-亚硝氨基）-1-（3-吡啶基）-1-丁酮（NNK）及其代谢物,了解小鼠体内NNK的代谢途径,利用Q Exactive轨道阱高分辨质谱仪,建立了一种同时检测C57BL/6小鼠血液中NNK及其7种代谢物[4-（N-甲基-N-亚硝氨基）-1-（3-吡啶基）-1-丁醇（NNAL）、NNK-N-氧化物（NNK-N-oxide）、NNAL-N-氧化物（NNAL-N-oxide）、4-羟基-1-（3-吡啶基）-1-丁酮（HPB）、1-（3-吡啶基）-1,4-二醇（PBD）、1-（3-吡啶基）-1-丁酮-4-羧酸（吡啶基丁酮酸）和1-（3-吡啶基）-1-丁醇-4-羧酸（吡啶基羟基酸）]的液相色谱-高分辨质谱（LC-HRMS）方法。以NNK-d4、NNAL-d3和HPB-d4为内标,小鼠血清样品经乙腈沉淀蛋白后,直接进行亲水相互作用色谱（HILIC）柱分离和质谱分析,质谱扫描模式采用一级全扫描和数据依赖二级扫描（Full MS/dd MS2）模式。结果表明：各目标物的定量限在0.042-0.263 ng/m之间,线性相关系数为0.999 1-1.000 0,加标回收率在89.2%-116.5%之间,日内精密度在1.54%-8.06%之间。该方法选择性好,分析效率高,目标物线性范围大,适合于小鼠血液中NNK及其代谢物检测与分析。

英文摘要：

In order to accurately determine levels of 4-（N-methyl-N-nitrosamino）-1-（3-pyridyl）-1-butanone（NNK） and its metabolites in mouse blood and the metabolic pathways of NNK in mice, a liquid chromatography-high resolution mass spectrometry（LC-HRMS） method for simultaneous determination of NNK and its seven metabolites [including 4-（N-methyl-N-nitrosamino）-1-（3-pyridyl）-1-butanol（NNAL）,NNK-N-oxide, NNAL-N-oxide, 4-hydroxy-1-（3-pyridyl）-1-butanone（HPB）, 1-（3-pyridyl）-1,4-diol（PBD）, 1-（3-pyridyl）-1-butanone-4-carboxylic acid and 1-（3-pyridyl）-1-butanol-4-carboxylic acid] in the blood ofC57BL/6 mice was established by Q Exactive Orbitrap High Resolution Mass Spectrometer. With NNK-d4,NNAL-d3, and HPB-d4 as internal standards, after protein precipitation with acetonitrile, the serum samples of C57BL/6 mice were separated by a HILIC column and determined by a mass spectrometer under full scan/data dependent MS2 mode. The results showed that the limits of quantification of the target analytes ranged from 0.042 to 0.263 ng/m L with correlation coefficients of 0.999 1 to 1.000 0, and the recoveries ranged from 89.2% to116.5% with the intra-day precision of 1.54% to 8.06%. The developed method features good selectivity, high efficiency and large linear range, and is suitable for the simultaneous determination of NNK and its seven metabolites in mouse blood.