title: Simultaneous determination of NNK and its seven metabolites in rabbit blood by hydrophilic interaction liquid chromatography-tandem mass spectrometry.
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.
authors.affiliation: Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China.
authors.forename: Hailei
authors.initials: H
authors.lastname: Lang
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Qidong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Baojun
authors.initials: B
authors.lastname: Cao
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.forename: Jianxun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000032:analysis* / Q000493:pharmacokinetics* / Q000633:toxicity; D002853:Chromatography, Liquid; D003497:Cyclic N-Oxides / Q000097:blood*; D057927:Hydrophobic and Hydrophilic Interactions; D006900:Hydroxylation; D057230:Limit of Detection; D008297:Male; D009602:Nitrosamines / Q000097:blood* / Q000493:pharmacokinetics* / Q000633:toxicity; D011725:Pyridines / Q000097:blood*; D011817:Rabbits; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: C526964:3-(4-(methylnitrosoamino)-1-hydroxybutyl)pyridine N-oxide; D002273:Carcinogens; D003497:Cyclic N-Oxides; D009602:Nitrosamines; D011725:Pyridines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol