Abstract
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.
The process of the experiment in this study. NNK solution was injected into rabbit body. Blood samples were obtained and processed, and then transferred into vials. NNK and its metabolites were separated by HILIC column. The ion source of MS is ESI and MRM mode was employed for monitoring ion pairs. The chromatogram of NNK and its metabolites was obtained.
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Acknowledgments
This work was supported by NSFC (Grant no. 21175153). The authors gratefully thank “Animal experimental center of Zhengzhou University.
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Lang, H., Wang, S., Zhang, Q. et al. Simultaneous determination of NNK and its seven metabolites in rabbit blood by hydrophilic interaction liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 405, 2083–2089 (2013). https://doi.org/10.1007/s00216-012-6641-z
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DOI: https://doi.org/10.1007/s00216-012-6641-z