Quantitative Determination of Ginsenoside Rg1 in Rat Plasma by Ultrahigh Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) and its Application in a Pharmacokinetics and Bioavailability Study

Author(s): Qinghua Weng, Zhenan Zhang, Linglong Chen, Weiwei You, Jinlai Liu, Feifei Li, Lianguo Chen*, Xiajuan Jiang*.

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 1 , 2020

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Abstract:

Background: Ginsenoside Rg1 (Rg1) is the main active compound of ginseng herbs.

Objective: The aim of this study is to develop a rapid, selective and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the levels of Rg1 in rat plasma and investigate the pharmacokinetics and bioavailability of Rg1 in rats.

Methods: Chromatographic separation was achieved on an UHPLC-MS/MS system with an UPLC BEH C18 column using an elution gradient of a mixture of acetonitrile and water (with 0.1% formic acid). The analytes were quantitatively determined by negative-mode electrospray tandem MS.

Results: The linearity of the calibration curve was from 2 to 1,000 ng/mL (r ≥ 0.9956), and the lower limit of quantification was 2 ng/mL. The inter-day and intra-day precision were both lower than 12.0%, and the accuracy ranged from 90.6 to 109.7%. The recovery of the targets was higher than 87.0%, and the matrix effect at three different analyte concentrations were from 89.0 to 97.2%. The bioavailability of Rg1 was only 6.1% due to a poor oral absorption.

Conclusion: This new quantitative method was found to be sensitive, rapid and selective, and was successfully used to study the pharmacokinetics of Rg1 after intravenous and oral administration in rats.

Keywords: Ginsenoside Rg1, pharmacokinetics, bioavailability, rat, plasma, UHPLC-MS/MS.

[1]
Zhu, G.; Wang, H.; Wang, T.; Shi, F. Ginsenoside Rg1 attenuates the inflammatory response in DSS-induced mice colitis. Int. Immunopharmacol., 2017, 50, 1-5.
[2]
Li, H.; Liu, B.; Li, P.; Feng, L.; Ma, H.; Xuan, S.; Cao, Y. Inhibitory effects of curcumin on inflammatory cytokines in rats with paraquat poisoning. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 2015, 33(9), 689-692.
[3]
Zhou, T.; Zu, G.; Zhang, X.; Wang, X.; Li, S.; Gong, X.; Liang, Z.; Zhao, J. Neuroprotective effects of ginsenoside Rg1 through the Wnt/beta-catenin signaling pathway in both in vivo and in vitro models of Parkinson’s disease. Neuropharmacology, 2016, 101, 480-489.
[4]
Wang, J.; Li, D.; Hou, J.; Lei, H. Protective effects of geniposide and ginsenoside Rg1 combination treatment on rats following cerebral ischemia are mediated via microglial microRNA1555p inhibition. Mol. Med. Rep., 2018, 17(2), 3186-3193.
[5]
Zu, G.; Guo, J.; Che, N.; Zhou, T.; Zhang, X.; Wang, G.; Ji, A.; Tian, X. Corrigendum: Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/beta-catenin pathway. Sci. Rep., 2017, 7, 45252.
[6]
Zhu, C.; Wang, Y.; Liu, H.; Mu, H.; Lu, Y.; Zhang, J.; Huang, J. Oral administration of Ginsenoside Rg1 prevents cardiac toxicity induced by doxorubicin in mice through anti-apoptosis. Oncotarget, 2017, 8(48), 83792-83801.
[7]
Qi, B.; Zhang, S.; Guo, D.; Guo, S.; Jiang, X.; Zhu, X. Protective effect and mechanism of ginsenoside Rg1 on carbon tetrachlorideinduced acute liver injury. Mol. Med. Rep., 2017, 16(3), 2814-2822.
[8]
Tian, W.; Chen, L.; Zhang, L.; Wang, B.; Li, X.B.; Fan, K.R.; Ai, C.H.; Xia, X.; Li, S.D.; Li, Y. Effects of ginsenoside Rg1 on glucose metabolism and liver injury in streptozotocin-induced type 2 diabetic rats. Genet. Mol. Res., 2017, 16(1)
[http://dx.doi.org/10.4238/gmr16019463]
[9]
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: A review. Arab. J. Chem., 2017, 10, S1409-S1421.
[10]
AlOthman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities, stability studies and degradation products. RASE, 2013, 2, 155-166.
[11]
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur., 2006, 11(1-2), 69-74.
[12]
Yue, L.; Zhu, D.N.; Yan, Y.Q.; Yu, B.Y. Relationship between components changes and efficacy of Shengmaisan VII. Chemical dynamic change of schisandrin in Shengmaisan. Zhongguo Zhongyao Zazhi, 2006, 31(12), 1010-1012.
[13]
Dong, L.; Zhang, C.Y.; Chen, S.L. HPLC-UV-ELSD characteristic figure and chemical pattern recognition of Panacis Quinquefolii Radix. Yao Xue Xue Bao, 2011, 46(2), 198-202.
[14]
Zhang, J.T.; Qu, Z.W.; Liu, Y.; Deng, H.L. Preliminary study on antiamnestic mechanism of ginsenoside Rg1 and Rb1. Chin. Med. J. (Engl.), 1990, 103(11), 932-938.
[15]
Zhan, S.; Shao, Q.; Fan, X.; Li, Z. Development of a sensitive LC-MS/MS method for simultaneous quantification of eleven constituents in rat serum and its application to a pharmacokinetic study of a Chinese medicine Shengmai injection. Biomed. Chromatogr., 2015, 29(2), 275-284.
[16]
Yu, J.; Gu, L.Q.; Xin, Y.F.; Gao, H.Y.; Xu, X.Z.; Zhang, S.; Zhou, G.L.; You, Z.Q.; Huo, L.R.; Xuan, Y.X. Simultaneous determination and pharmacokinetics of eight ginsenosides by LC-MS/MS after intravenously infusion of ‘SHENMAI’ injection in dogs. Pak. J. Pharm. Sci., 2017, 30(2), 421-427.
[17]
Feng, L.; Hu, C.J.; Yu, L.Y. Pharmacokinetics of ginsenosides Rg1 and its metabolites in rats. Yao Xue Xue Bao, 2010, 45(5), 636-640.
[18]
Wu, X.; You, Y.; Qu, G.; Ma, R.; Zhang, M. Simultaneous determination of ginsenoside Rb1, ginsenoside Rg1, paeoniflorin, albiflorin and oxypaeoniflorin in rat plasma by liquid chromatography-tandem mass spectrometry: Application to a pharmacokinetic study of wen-Yang-Huo-Xue soft capsule. Biomed. Chromatogr., 2017, 31(12) Epub 2017 Jul 26.
[http://dx.doi.org/10.1002/bmc.4019]
[19]
He, C.; Feng, R.; Sun, Y.; Chu, S.; Chen, J.; Ma, C.; Fu, J.; Zhao, Z.; Huang, M.; Shou, J.; Li, X.; Wang, Y.; Hu, J.; Wang, Y.; Zhang, J. Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC-MS/MS: Rg1 excretion in rat bile, urine and feces. Acta Pharm. Sin. B, 2016, 6(6), 593-599.
[20]
Chen, L.G.; Wang, Z.; Wang, S.; Li, T.; Pan, Y.; Lai, X. Determination of apremilast in rat plasma by UPLC-MS-MS and its application to a pharmacokinetic study. J. Chromatogr. Sci., 2016, 54(8), 1336-1340.
[21]
Xiong, J.H.; Ye, H.; Lin, Y.X.; Yang, J.Z.; Chen, D.W.; Yu, D.G.; Chen, L.G. Determining concentrations of icotinib in plasma of rat by UPLC method with ultraviolet detection: applications for pharmacokinetic studies. Curr. Pharmaceut. Anal., 2017, 13(4), 340-344.
[22]
Peng, Y.; Wu, Z.; Huo, Y.; Chen, Y.; Lu, F.; Peng, Q.; Liang, Y. Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC-MS/MS: Rg1 excretion in rat bile, urine and feces. Analytical. Methods, 2017, 37(9), 5441-5448.
[23]
Li, X.; Wang, G.; Sun, J.; Hao, H.; Xiong, Y.; Yan, B.; Zheng, Y.; Sheng, L. Pharmacokinetic and absolute bioavailability study of total panax notoginsenoside, a typical multiple constituent traditional chinese medicine (TCM) in rats. Biol. Pharm. Bull., 2007, 30(5), 847-851.
[24]
Liu, R.; Xing, D.; Lu, H.; Wu, H.; Du, L. Pharmacokinetics of puerarin and ginsenoside Rg1 of CBN injection and the relation with platelet aggregation in rats. Am. J. Chin. Med., 2006, 34(6), 1037-1045.
[25]
Ansong, C.; Ortega, C.; Payne, S.H.; Haft, D.H.; Chauvigne-Hines, L.M.; Lewis, M.P.; Ollodart, A.R.; Purvine, S.O.; Shukla, A.K.; Fortuin, S.; Smith, R.D.; Adkins, J.N.; Grundner, C.; Wright, A.T. Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis. Chem. Biol., 2013, 20(1), 123-133.
[26]
Chen, L.; Weng, Q.; Li, F.; Liu, J.; Zhang, X.; Zhou, Y. Pharmacokinetics and bioavailability study of tubeimoside I in ICR mice by UPLC-MS/MS. J. Anal. Methods Chem., 2018, 20189074893
[27]
Ye, W.; Chen, R.; Sun, W.; Huang, C.; Lin, X.; Dong, Y.; Wen, C.; Wang, X. Determination and pharmacokinetics of engeletin in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1060, 144-149.
[28]
Ma, J.S.; Wang, S.H.; Huang, X.L.; Geng, P.W.; Wen, C.C.; Zhou, Y.F.; Yu, L.S.; Wang, X.Q. Validated UPLC-MS/MS method for determination of hordenine in rat plasma and its application to pharmacokinetic study. J. Pharmaceut. Biomed. Anal., 2015, 111, 131-137.
[29]
Wang, X.Q.; Wang, S.H.; Lin, F.Y.; Zhang, Q.W.; Chen, H.L.; Wang, X.C.; Wen, C.C.; Ma, J.S.; Hu, L.F. Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC-MS/MS. J. Chromatogr. B-Analytical. Technol. Biomed. Life Sci., 2015, 983, 125-131.
[30]
Wang, S.; Wu, H.; Huang, X.; Geng, P.; Wen, C.; Ma, J.; Zhou, Y.; Wang, X. Determination of N-methylcytisine in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 990, 118-124.
[31]
Zhang, Q.; Wen, C.; Xiang, Z.; Ma, J.; Wang, X. Determination of CUDC-101 in rat plasma by liquid chromatography mass spectrometry and its application to a pharmacokinetic study. J. Pharm. Biomed. Anal., 2014, 90, 134-138.


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Article Details

VOLUME: 16
ISSUE: 1
Year: 2020
Page: [85 - 91]
Pages: 7
DOI: 10.2174/1573412915666181109092728
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