Generic placeholder image

Drug Metabolism and Bioanalysis Letters

Editor-in-Chief

ISSN (Print): 2949-6810
ISSN (Online): 2949-6829

Research Article

Simultaneous Determination of 16-Hydroxystrychnine and Demethylbrucine by LC-MS/MS in Rat Urine and Its Application to Pharmacokinetic Study

Author(s): Rui Yan*, Bin Xia and Shan Zhang

Volume 16, Issue 1, 2023

Published on: 15 May, 2023

Page: [59 - 64] Pages: 6

DOI: 10.2174/1872312815666230427122212

Price: $65

conference banner
Abstract

Introduction: This paper aimed to establish a method to help investigate the combination mechanism of traditional Chinese medicine from the metabolic perspective.

Background: Semen Strychni has been a frequently used herb in clinics for a long time. In traditional Chinese medical science, Semen Strychni always combinate with other herbs to modulate its nature of severe toxicity. However, the mechanism of the combination is still unclear. Previous research mostly focused on the components of the herbs. The metabolic processes of the main components of the Semen Strychni are also very important and have rarely been reported.

Objective: This study tended to develop a rapid and sensitive high-performance liquid chromatographic- tandem mass spectrometric (HPLC-MS/MS) method for the determination of two major metabolites of Semen Strychni in rat urine.

Methods: Chromatographic separation was carried out on a C18 column. Detection was performed by a selective reaction monitoring (SRM) mode via an electrospray ionization (ESI) source operating in the positive ionization mode. Analysis of analytes from rat plasma was carried out by protein precipitation using acetonitrile.

Results: The assay was validated in terms of specificity, precision, recovery, etc. The intra- and inter-day precision values were less than 13.1%. The recoveries at three levels were more than 69.1%. The method was then used to study the kinetic profiles of the metabolites of Semen Strychni in rat urine for the first time.

Conclusion: The results demonstrate that the established LC/MS method in this study is accurate and sensitive for the simultaneous determination of the two metabolites of Semen Strychni in rats' urine samples. This method could be a supplement to the plasma pharmacokinetics of Semen Strychni.

Graphical Abstract

[1]
Deng, X.K.; Yin, W.; Li, W.D.; Yin, F.Z.; Lu, X.Y.; Zhang, X.C.; Hua, Z.C.; Cai, B.C. The anti-tumor effects of alkaloids from the seeds of Strychnos nux-vomica on HepG2 cells and its possible mechanism. J. Ethnopharmacol., 2006, 106(2), 179-186.
[http://dx.doi.org/10.1016/j.jep.2005.12.021] [PMID: 16442763]
[2]
Duverneuil, C.; Grandmaison, G.L.; Mazancourt, P.; Alvarez, J.C. Liquid chromatography/photodiode array detection for determination of strychnine in blood: A fatal case report. Forensic Sci. Int., 2004, 141(1), 17-21.
[http://dx.doi.org/10.1016/j.forsciint.2003.12.010] [PMID: 15066709]
[3]
Lu, M.; Hu, Q.; Zhang, Y.; Zhai, Y.; Zhou, Y.; Jiang, J. Comparative chemical profiling of three TCM drugs in the Paeoniaceae family by UPLC-MS/MS combined with chemometric methods. Biochem. Syst. Ecol., 2019, 83, 121-129.
[http://dx.doi.org/10.1016/j.bse.2019.02.002]
[4]
Wang, P.; Li, K.; Tao, Y.; Li, D.; Zhang, Y.; Xu, H.; Yang, H. TCM-ADMEpred: A novel strategy for poly-pharmacokinetics prediction of traditional Chinese medicine based on single constituent pharmacokinetics, structural similarity, and mathematical modeling. J. Ethnopharmacol., 2019, 236, 277-287.
[http://dx.doi.org/10.1016/j.jep.2018.07.008] [PMID: 30826421]
[5]
Ding, Z.; Zhong, R.; Yang, Y.; Xia, T.; Wang, W.; Wang, Y.; Xing, N.; Luo, Y.; Li, S.; Shang, L.; Shu, Z. Systems pharmacology reveals the mechanism of activity of Ge-Gen-Qin-Lian decoction against LPS-induced acute lung injury: A novel strategy for exploring active components and effective mechanism of TCM formulae. Pharmacol. Res., 2020, 156, 104759.
[http://dx.doi.org/10.1016/j.phrs.2020.104759] [PMID: 32200026]
[6]
China Pharmacopoeia Committee. Chinese Pharmacopoeia; Chemical Industry Press: Beijing, 2015, 1, p. 475.
[7]
Lin, A.; Su, X.; She, D.; Qiu, K.; He, Q.; Liu, Y. LC–MS/MS determination and comparative pharmacokinetics of strychnine, brucine and their metabolites in rat plasma after intragastric administration of each monomer and the total alkaloids from Semen Strychni. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2016, 1008, 65-73.
[http://dx.doi.org/10.1016/j.jchromb.2015.11.012] [PMID: 26625339]
[8]
Chen, X.; Lai, Y.; Cai, Z. Simultaneous analysis of strychnine and brucine and their major metabolites by liquid chromatography-electrospray ion trap mass spectrometry. J. Anal. Toxicol., 2012, 36(3), 171-176.
[http://dx.doi.org/10.1093/jat/bks004] [PMID: 22417832]
[9]
Gu, W.; Wang, D.; Pan, Z.; Liu, X.; Cai, B.; Chen, J. Ultra-performance liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of brucine, strychnine and brucine N -oxide in rat plasma: Application to a pharmacokinetic study. Biomed. Chromatogr., 2016, 30(7), 1097-1103.
[http://dx.doi.org/10.1002/bmc.3656] [PMID: 26578094]
[10]
Liu, Y.; Zhu, R.; Li, H.; Yan, M.; Lei, Y. Ultra-performance liquid chromatography–tandem mass spectrometric method for the determination of strychnine and brucine in mice plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2011, 879(26), 2714-2719.
[http://dx.doi.org/10.1016/j.jchromb.2011.07.033] [PMID: 21855426]
[11]
Xu, Y.; Si, D.; Liu, C. Determination of strychnine and brucine in rat plasma using liquid chromatography electrospray ionization mass spectrometry. J. Pharm. Biomed. Anal., 2009, 49(2), 487-491.
[http://dx.doi.org/10.1016/j.jpba.2008.10.020] [PMID: 19062219]
[12]
Tian, J.X.; Peng, C.; Xu, L.; Tian, Y.; Zhang, Z.J. In vitro metabolism study of Strychnos alkaloids using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry. Biomed. Chromatogr., 2013, 27(6), 775-783.
[http://dx.doi.org/10.1002/bmc.2860] [PMID: 23348426]
[13]
Tanimoto, Y.; Ohkuma, T.; Oguri, K.; Yoshimura, H. A novel metabolite of strychnine, 22-hydroxystrychnine. Xenobiotica, 1991, 21(3), 395-402.
[http://dx.doi.org/10.3109/00498259109039479] [PMID: 1862661]
[14]
Guo, J.F.; Chen, X.Y.; Zhong, D.F. Identification of strychnine, brucine and their metabolites in body fluids by liquid chromatography - electrospray ion trap mass spectrometry. Yaowu Fenxi Zazhi, 2001, 21(3), 167-170.
[15]
Xu, J.; Yan, R. Determination of the metabolite of ephedrine, 4-Hydroxyephedrine, by LC–MS-MS in rat urine and its application in excretion profiles after oral administration of Ephedra sinica Stapf and processing Ephedra sinica Stapf. J. Chromatogr. Sci., 2017, 55(2), 162-165.
[http://dx.doi.org/10.1093/chromsci/bmw165] [PMID: 27733484]
[16]
Yan, F.; He, H.; Yan, R. Relative determination of the alkaloid metabolites of Er Miao San in rat urine by LC–MS/MS and its application to pharmacokinetics. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 951-952, 38-43.
[http://dx.doi.org/10.1016/j.jchromb.2014.01.015] [PMID: 24508675]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy