title: UPLC-MS/MS method for the determination of tobacco-specific biomarker NNAL, tamoxifen and its main metabolites in rat plasma.
abstract: Cigarette smoke is known to interact with tamoxifen-metabolizing enzymes and transporters and potentially affect its treatment outcome. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) because it is frequently used as a biomarker to assess human smoke exposure. In order to study the potential pharmacokinetic interaction between cigarette smoke and tamoxifen in rats a UPLC-MS/MS method for the simultaneous determination of NNAL and tamoxifen along with its metabolites in rat plasma has been developed and validated. Analytes were extracted with methanol and separated on a HSS T3 column by a gradient elution with the mobile phase consisting of acetonitrile and water. The lower limits of quantitation ranged from 0.05 to 0.62 ng/mL. Precisions showed RSD <15.8% and accuracy in the range 80.6-116.0%. Mean analyte recoveries ranged from 76.9 to 108.4%. The method was successfully applied to study the effects of cigarette smoke condensate (CSC), NNK and benzo(a)pyrene pre-treatment on the pharmacokinetics of tamoxifen and its metabolites in rats. Significant effects of CSC, NNK, benzo(a)pyrene were observed on pharmacokinetics of tamoxifen and its metabolites. We also found that plasma NNAL levels are statistically significant correlated with plasma 4-hydroxy-tamoxifen and endoxifen.
authors.affiliation: Department of Clinical Pharmacy, Pharmacy School of Sichuan University, Chengdu, Sichuan, China.|Sichuan Tobacco Quality Supervision and Testing Station, Chengdu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Clinical Pharmacy, Pharmacy School of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Clinical Pharmacy, Pharmacy School of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, Pharmacy School of Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D057230:Limit of Detection; D009602:Nitrosamines / Q000097:blood*; D011725:Pyridines / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013629:Tamoxifen / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D009602:Nitrosamines; D011725:Pyridines; D013629:Tamoxifen; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol
keywords: 4-hydroxy-tamoxifen; UPLC-MS/MS; cigarette smoke; endoxifen; rats plasma