Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry

Jing Yang; Steven G. Carmella; Stephen S. Hecht

doi:10.1016/j.jchromb.2017.01.008

Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry

Jing Yang, Steven G. Carmella, Stephen S. Hecht

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

We have developed a chiral stationary phase liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry (LC–NSI–HRMS/MS) method to investigate the enantiomeric composition of low parts per trillion amounts of the carcinogen N'-nitrosonornicotine (NNN) in the urine of cigarette smokers and smokeless tobacco users. (S)-NNN is the major enantiomer in tobacco and is more carcinogenic than (R)-NNN in rats, but no data are available on the enantiomeric composition of NNN in humans. The method used [¹³C₆]NNN as an internal standard and [pyridine-D₄]nornicotine to monitor possible artifactual formation of NNN, which was found to be less than 2% of the quantified NNN. The enantiomeric composition of NNN (20.5 ± 27.1 fmol/mL urine) in 20 cigarette smokers was 67 ± 5% (S)-NNN while that in 10 smokeless tobacco users (67.1 ± 56.7 fmol/mL urine) was 56 ± 3% (S)-NNN. These results demonstrate that the highly carcinogenic (S)-NNN is the major enantiomer in human urine, and that the enantiomeric composition of NNN in human urine is remarkably similar to that in cigarette smoke and smokeless tobacco. This is the first study to combine chiral stationary phase separations with nanoelectrospray ionization and high resolution tandem mass spectrometry to quantify trace levels of enantiomeric metabolites in human urine.

Original language	English (US)
Pages (from-to)	127-131
Number of pages	5
Journal	Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume	1044-1045
DOIs	https://doi.org/10.1016/j.jchromb.2017.01.008
State	Published - Feb 15 2017

Bibliographical note

Funding Information:
This work was supported by the National Cancer Institute [grant number R01-CA081301] and by a supplement from the U.S. Food and Drug Administration. Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, funded in part by a National Cancer Institute Cancer Center Support Grant [grant number P01-CA77598].

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

Chiral separation
Chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry
Enantiomeric composition
N'-Nitrosonornicotine
Smokeless tobacco user's urine
Smoker's urine

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10.1016/j.jchromb.2017.01.008

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296371

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Yang, J., Carmella, S. G., & Hecht, S. S. (2017). Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1044-1045, 127-131. https://doi.org/10.1016/j.jchromb.2017.01.008

Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry. / Yang, Jing; Carmella, Steven G.; Hecht, Stephen S.
In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1044-1045, 15.02.2017, p. 127-131.

Research output: Contribution to journal › Article › peer-review

Yang, J, Carmella, SG & Hecht, SS 2017, 'Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry', Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 1044-1045, pp. 127-131. https://doi.org/10.1016/j.jchromb.2017.01.008

Yang J, Carmella SG , Hecht SS. Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2017 Feb 15;1044-1045:127-131. doi: 10.1016/j.jchromb.2017.01.008

Yang, Jing ; Carmella, Steven G. ; Hecht, Stephen S. / Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry. In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2017 ; Vol. 1044-1045. pp. 127-131.

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abstract = "We have developed a chiral stationary phase liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry (LC–NSI–HRMS/MS) method to investigate the enantiomeric composition of low parts per trillion amounts of the carcinogen N'-nitrosonornicotine (NNN) in the urine of cigarette smokers and smokeless tobacco users. (S)-NNN is the major enantiomer in tobacco and is more carcinogenic than (R)-NNN in rats, but no data are available on the enantiomeric composition of NNN in humans. The method used [13C6]NNN as an internal standard and [pyridine-D4]nornicotine to monitor possible artifactual formation of NNN, which was found to be less than 2% of the quantified NNN. The enantiomeric composition of NNN (20.5 ± 27.1 fmol/mL urine) in 20 cigarette smokers was 67 ± 5% (S)-NNN while that in 10 smokeless tobacco users (67.1 ± 56.7 fmol/mL urine) was 56 ± 3% (S)-NNN. These results demonstrate that the highly carcinogenic (S)-NNN is the major enantiomer in human urine, and that the enantiomeric composition of NNN in human urine is remarkably similar to that in cigarette smoke and smokeless tobacco. This is the first study to combine chiral stationary phase separations with nanoelectrospray ionization and high resolution tandem mass spectrometry to quantify trace levels of enantiomeric metabolites in human urine.",

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Analysis of N′-nitrosonornicotine enantiomers in human urine by chiral stationary phase liquid chromatography–nanoelectrospray ionization–high resolution tandem mass spectrometry

Abstract

Bibliographical note

Keywords

Access

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