Skip to main content
SpringerLink
Log in

Identification of In Vivo Metabolites of Levophencynonate in Human Plasma and Urine by High-Performance Liquid Chromatography Tandem Triple-Time-of-Flight Mass Spectrometry

  • Original
  • Published:
Chromatographia Aims and scope Submit manuscript

Abstract

Levophencynonate is an anticholinergic agent which can prevent acute motion sickness with an efficacy similar to scopolamine. It will take effect by competitive binding to central muscarinic acetylcholine receptors. Previously, there was only one investigation about metabolites of phencynonate in rats and ten metabolites have been found. A HPLC/Triple TOF MS method was established and successfully applied to investigate the in vivo metabolites of levophencynonate after a 2 mg levophencynonate hydrochloride tablet was administrated to healthy volunteers. A total of 13 metabolites were found in human specimens, including six from plasma and all of 13 from urine. The metabolites consisted of phase I and phase II products, including demethylation (M1), demethylation/oxidation (M2, M3, M4, and M5), demethylation/methylene to ketone (M6, M7), oxidation (M8, M9), desaturation (M10), demethylation/desaturation (M11), di-oxidation (M12), and oxidation/glucuronidation (M13) metabolites. Products of demethylation (M1), demethylation/desaturation (M11), and oxidation/glucuronidation (M13) were the main metabolites with higher intensity than the others. These findings would provide an important basis for the clinical application and further study of levophencynonate. In addition to the feasibility of the HPLC/Triple TOF MS approach for rapid and reliable characterization of metabolites, the identifications of precise structures of these metabolites need to be confirmed by other techniques, such as 1H and 13C NMR, and in order to elucidate a more detailed metabolic profile of levophencynonate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Xu GZ, Cai ZJ, Dong L, Huang CY, Liu WW, Zhao RB, An DY, Xu XR, Wang SF, Wang HB (1993) Chin J Clin Pharmacol 9:65–74

    CAS  Google Scholar 

  2. Dai JG, Liu CG, Yu LS, Yang AZ, Jia HB, Bi HZ, Wang KN (1997) Chin J Aerosp Med 8:10–14

    Google Scholar 

  3. Deng YL, Zhang YM (2001) Chin J New Drugs 10:453–454

    Google Scholar 

  4. Wang LY, Wang Y, Zheng JQ, Zhong BH, Liu H, Dong SJ, Ruan JX, Liu KL (2005) Acta Pharmacol Sin 26:527–532. doi:10.1111/j.1745-7254.2005.00089.x

    Article  CAS  Google Scholar 

  5. Liu Y, Kou Y, Xue M, Xu Y, He L, Ruan J, Liu K (2010) Talanta 82:1200–1211. doi:10.1016/j.talanta.2010.06.032

    Article  CAS  Google Scholar 

  6. Lu C, Wang Y, Sheng Z, Liu G, Fu Z, Zhao J, Zhao J, Yan X, Zhu B, Peng S (2010) Toxicol Appl Pharmacol 248:178–184. doi:10.1016/j.taap.2010.07.020

    Article  CAS  Google Scholar 

  7. Qian Q, Li S-L, Sun E, Zhang K-R, Tan X-B, Wei Y-J, Fan H-W, Cui L, Jia X-B (2012) J Pharm Biomed Anal 66:392–398. doi:10.1016/j.jpba.2012.03.053

    Article  CAS  Google Scholar 

  8. Zha W, A J, Wang G, Yan B, Gu S, Zhu X, Hao H, Huang Q, Sun J, Zhang Y, Cao B, Ren H (2009) Biomarkers 14:372–380. doi:10.1080/13547500903026401

    Article  CAS  Google Scholar 

  9. Huck CW (2001) Bonn GnK. Phytochem Anal 12:104–109. doi:10.1002/pca.547

    Article  CAS  Google Scholar 

  10. Balderas C, Villaseñor A, García A, Rupérez FJ, Ibañez E, Señorans J, Guerrero-Fernández J, González-Casado I, Gracia-Bouthelier R, Barbas C (2010) J Pharm Biomed Anal 53:1298–1304. doi:10.1016/j.jpba.2010.07.034

    Article  CAS  Google Scholar 

  11. Xiong A, Yang L, He Y, Zhang F, Wang J, Han H, Wang C, Bligh SWA, Wang Z (2009) Rapid Commun Mass Spectrom 23:3907–3916. doi:10.1002/rcm.4329

    Article  CAS  Google Scholar 

  12. Teunissen SF, Rosing H, Schinkel AH, Schellens JHM, Beijnen JH (2010) J Chromatogr B 878:3199–3216. doi:10.1016/j.jchromb.2010.10.018

    Article  CAS  Google Scholar 

  13. Arumugam K, Chamallamudi MR, Gilibili RR, Mullangi R, Ganesan S, Kar SS, Averineni R, Shavi G, Udupa N (2011) Biomed Chromatogr 25:353–361. doi:10.1002/bmc.1455

    Article  CAS  Google Scholar 

  14. Han H, Yang L, Xu Y, Ding Y, Bligh SWA, Zhang T, Wang Z (2011) Rapid Commun Mass Spectrom 25:3339–3350. doi:10.1002/rcm.5216

    Article  CAS  Google Scholar 

  15. Lee SH, Yang HO, Kwon HC, Jung BH (2012) J Chromatogr B 906:33–40. doi:10.1016/j.jchromb.2012.08.015

    Article  CAS  Google Scholar 

  16. Xiao JF, Zhou B, Ressom HW (2012) TrAC Trends Anal Chem 32:1–14. doi:10.1016/j.trac.2011.08.009

    Article  Google Scholar 

  17. Elyashberg M (2015) TrAC Trends Anal Chem 69:88–97. doi:10.1016/j.trac.2015.02.014

    Article  CAS  Google Scholar 

  18. Wolfender J-L, Rudaz S, Choi YH, Kim HK (2013) Curr Med Chem 20:1056–1090. doi:10.2174/0929867311320080009

    CAS  Google Scholar 

  19. Dias D, Jones O, Beale D, Boughton B, Benheim D, Kouremenos K, Wolfender J-L, Wishart D (2016) Metabolites 6:46. doi:10.3390/metabo6040046

    Article  Google Scholar 

  20. Li B, Qi W, Shi A, Hu X, Cheng G (2016) J Chromatogr B 1027:221–226. doi:10.1016/j.jchromb.2016.05.054

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China

    Bo Li & Gang Cheng

  2. Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology, Beijing Hospital, Beijing, 100730, China

    Bo Li, Aixin Shi & Wenyuan Qi

  3. Shanghai AB Sciex Analytical Instrument Trading Co., Ltd, Beijing, 100015, China

    Dandan Si

Authors
  1. Bo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aixin Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dandan Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenyuan Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gang Cheng or Wenyuan Qi.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Beijing Hospital (Beijing, China) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The approval notice number of this research was 2013BJYYEC-050-02. In this study, a total of ten healthy volunteers were enrolled after signing the Informed Consent Forms.

Funding

There was no funding for this research.

Conflict of interest

No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, B., Shi, A., Si, D. et al. Identification of In Vivo Metabolites of Levophencynonate in Human Plasma and Urine by High-Performance Liquid Chromatography Tandem Triple-Time-of-Flight Mass Spectrometry. Chromatographia 80, 417–426 (2017). https://doi.org/10.1007/s10337-017-3264-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10337-017-3264-8

Keywords

Search

Navigation