Analysis of N′-nitrosonornicotine and its metabolites in rabbit blood with liquid chromatography/tandem mass spectrometric method

A hydrophilic interaction liquid chromatographic-tandem mass spectrometric (HILIC-MS-MS) method for investigation of the in vivo metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen, in rabbit blood has been developed and validated. This method achieved excellent repeatability and accuracy. Recovery ranged from 76.9 to 116.3 % and precision (as RSD) between 0.53 and 6.52 %. Linearity was good for all compounds (R(2)>0.9990) and the limit of detection (LOD) ranged from 0.016 to 0.082 ng mL(-1). Pharmacokinetic analysis indicated that NNK was rapidly eliminated in vivo in rabbit blood and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was the major metabolite. The hydroxy acid, keto acid, and NNAL-N-oxide were also important metabolites in rabbit blood. It is probable that α-methylene hydroxylation was the major pathway of α-hydroxylation of NNK and NNAL in the rabbit.

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Simultaneous determination of NNK and its seven metabolites in rabbit blood by hydrophilic interaction liquid chromatography–tandem mass spectrometry

Lang

Zhang

Zhao

et al. 2013

Anal Bioanal Chem

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Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung

et al. 2014

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A hydrophilic-interaction liquid chromatography-tandem mass spectrometry (HILIC-MS-MS) method was developed for the determination of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolites in mouse liver and lung. The limits of detection of all analytes were in the range 0.017-0.057 ng mL(-1), and recovery ranged from 88.4-119.8 % with intra and inter-day precision in the range 0.89-6.03 % and 1.01-6.97 %, respectively. This simple and accurate method was used to evaluate the effect of chronic alcohol consumption on NNK bioactivation in mouse tissue. Time-course curves for NNK and its metabolites were generated, and the areas under the curves (AUCs) were compared. It was found that target tissues of NNK carcinogenesis in C57BL/6 mice contained high levels of α-hydroxylation metabolites of NNK and its carbonyl reduction metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The most pronounced effect of alcohol was to enhance α-hydroxylation of NNK in mouse lung and liver, which suggests that chronic alcohol consumption may increase the risk of carcinogenicity associated with NNK in mice.

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A simple and highly sensitive UPLC-ESI-MS/MS method for the simultaneous quantification of nicotine, cotinine, and the tobacco-specific carcinogens N’-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in serum samples

Loukotková

VonTungeln

Vanlandingham

et al. 2018

Journal of Chromatography B

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Analysis of N′-nitrosonornicotine and its metabolites in rabbit blood with liquid chromatography/tandem mass spectrometric method

Cited by 3 publications

References 12 publications

Simultaneous determination of NNK and its seven metabolites in rabbit blood by hydrophilic interaction liquid chromatography–tandem mass spectrometry

Simultaneous determination of NNK and its seven metabolites in rabbit blood by hydrophilic interaction liquid chromatography–tandem mass spectrometry

Simultaneous determination of NNK and its metabolites in mouse tissue for evaluating the effects of chronic alcohol consumption on the metabolism of NNK in mouse liver and lung

A simple and highly sensitive UPLC-ESI-MS/MS method for the simultaneous quantification of nicotine, cotinine, and the tobacco-specific carcinogens N’-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in serum samples

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