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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Simultaneous Determination of Koumine and Gelsemine in Human Plasma Using HPLC-UV Assay and Its Clinical Application

Author(s): Hongqiang Qiu*, Changxi Yu*, Yu Cheng, Wancai Que, Xiaofang Zeng, Hui Wang and Maobai Liu

Volume 15, Issue 6, 2019

Page: [640 - 649] Pages: 10

DOI: 10.2174/1573412915666190222161942

open access plus

Abstract

Background: Of two main alkaloids extracted from Gelsemium, koumine was shown to be a promising analgesic, while gelsemine proved to be deleterious. Many patients suspected to be poisoned by Gelsemium cannot be timely diagnosed due to the lack of UPLC-MS/MS. Additionally, the concentration of alkaloids in humans has never been reported. The aim of this study was to establish a more economical and accessible method using HPLC-UV for diagnosis and quantitative analysis of Gelsemium poisoning.

Methods: Plasma spiked with an internal standard, oxcarbazepine, was prepared with solid-phase extraction. Koumine and gelsemine were separated on a C18 column using a mobile phase consisting of methanol, water, and di-n-butylamine (58:42:0.01) pumped at a flow rate of 1.00 mL/min. The detection wavelength was set at 263 nm. Plasma concentrations of two different times were determined for the patients.

Results: The calibration curves for both monomers possessed good linearity from 0.05-50 mg/L (r=0.9997 and 0.9999, respectively). The extraction recoveries were greater than 88.5 %. Variation for intraday and interday assays of koumine and gelsemine were less than 8.3% and 7.7%, respectively. The concentrations of the two alkaloids were identified in 5 patients with Gelsemium poisoning by using the established method.

Conclusion: The established method by using HPLC-UV is applicable for diagnosis and quantitative analysis of Gelsemium poisoning in such cases. TDM of koumine and gelsemine in patients with Gelsemium poisoning may provide additional information for the clinic to improve rescue strategy.

Keywords: Gelsemium, koumine, gelsemine, poisoning, toxicity, determination, concentration, HPLC.

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[1]
Dutt, V.; Thakur, S.; Dhar, V.J.; Sharma, A. The genus Gelsemium: An update. Pharmacogn. Rev., 2010, 4, 185-194.
[2]
Jin, G.L.; Su, Y.P.; Liu, M.; Xu, Y.; Yang, J.; Liao, K.J.; Yu, C.X. Medicinal plants of the genus Gelsemium (Gelsemiaceae, Gentianales)- a review of their phytochemistry, pharmacology, toxicology and traditional use. J. Ethnopharmacol., 2014, 152, 33-52.
[3]
Dutt, V.; Dhar, V.J.; Sharma, A. Antianxiety activity of Gelsemium sempervirens. Pharm. Biol., 2010, 48, 1091-1096.
[4]
Magnani, P.; Conforti, A.; Zanolin, E.; Marzotto, M.; Bellavite, P. Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice. Psychopharmacology (Berl.), 2010, 210, 533-545.
[5]
Ling, Q.; Liu, M.; Wu, M.X.; Xu, Y.; Yang, J.; Huang, H.H.; Yu, C.X. Anti-allodynic and neuroprotective effects of koumine, a Benth alkaloid, in a rat model of diabetic neuropathy. Biol. Pharm. Bull., 2014, 37, 858-864.
[6]
Lu, J.M.; Qi, Q.Z.; Liu, G.L.; Shen, Z.Y. KC, T. Effect of Gelsemium elegans Benth. injection on proliferation of tumor cells. Chin. J. Cancer, 1990, 9, 472-477.
[7]
Zhang, X.; Chen, Y.; Gao, B.; Luo, D.; Wen, Y.; Ma, X. Apoptotic effect of koumine on human breast cancer cells and the mechanism involved. Cell Biochem. Biophys., 2015, 72, 411-416.
[8]
Yuan, Z.; Matias, F.B.; Wu, J.; Liang, Z.; Sun, Z. Koumine attenuates lipopolysaccaride-stimulated inflammation in RAW264.7 Macrophages, coincidentally associated with inhibition of NF-kappaB, ERK and p38 pathways. Int. J. Mol. Sci., 2016, 17, 430.
[9]
Yuan, Z.H.; Liang, Z.E.; Wu, J.; Yi, J.E.; Chen, X.J.; Sun, Z.L. A potential mechanism for the anti-apoptotic property of koumine involving mitochondrial pathway in LPS-mediated RAW 264.7 Macrophages. Molecules, 2016, 21, 1317.
[10]
Qiu, H.Q.; Xu, Y.; Jin, G.L.; Yang, J.; Liu, M.; Li, S.P.; Yu, C.X. Koumine enhances spinal cord 3alpha-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain. Mol. Pain, 2015, 11, 46.
[11]
Yang, J.; Cai, H.D.; Zeng, Y.L.; Chen, Z.H.; Fang, M.H.; Su, Y.P.; Huang, H.H.; Xu, Y.; Yu, C.X. Effects of koumine on adjuvant-and collagen-induced arthritis in rats. J. Nat. Prod., 2016, 79, 2635-2643.
[12]
Jin, G.L.; Yue, R.C.; He, S.D.; Hong, L.M.; Xu, Y.; Yu, C.X. Koumine decreases astrocyte-mediated neuroinflammation and enhances autophagy, contributing to neuropathic pain from chronic constriction injury in rats. Front. Pharmacol., 2018, 9, 989.
[13]
Jin, G.L.; Yang, J.; Chen, W.Q.; Wang, J.; Qiu, H.Q.; Xu, Y.; Yu, C.X. The analgesic effect and possible mechanisms by which koumine alters type II collagen-induced arthritis in rats. J. Nat. Med., 2018, 73, 217-225.
[14]
Zhou, Z.; Wu, L.; Zhong, Y.; Fang, X.; Liu, Y.; Chen, H.; Zhang, W. Gelsemium elegans poisoning: a case with 8 months of follow-up and review of the literature. Front. Neurol., 2017, 8, 204.
[15]
Xiang, H.; Zhou, Y.J.; Huang, P.L.; Yu, C.N.; Liu, J.; Liu, L.Y.; He, P. Lethal poisoning with Gelsemium elegans in Guizhou, China. Public Health, 2016, 136, 185-187.
[16]
Chen, J.Z.; Li, Y.; Xiao, J.P.; Wu, S.S.; Song, H.W. Development of a sensitive and rapid UPLC-MS/MS method for the determination of koumine in rat plasma: Application to a pharmacokinetic study. Biomed. Chromatogr., 2013, 27, 736-740.
[17]
Zhang, S.; Hu, S.; Yang, X.; Shen, J.; Zheng, X.; Huang, K.; Xiang, Z. Development of a liquid chromatography with mass spectrometry method for the determination of gelsemine in rat plasma and tissue: Application to a pharmacokinetic and tissue distribution study. J. Sep. Sci., 2015, 38, 936-942.
[18]
Ji, S.J.; Liu, W. Simultaneous quantitative analysis of koumine, gelsemine and gelsenicine in biological samples. Fa Yi Xue Za Zhi, 2017, 33, 141-147.
[19]
Yang, K.; Long, X.M.; Liu, Y.C.; Chen, F.H.; Liu, X.F.; Sun, Z.L.; Liu, Z.Y. Development and in-house validation of a sensitive LC-MS/MS method for simultaneous quantification of gelsemine, koumine and humantenmine in porcine plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1076, 54-60.
[20]
Wang, L.; Wen, Y.; Meng, F. Simultaneous determination of gelsemine and koumine in rat plasma by UPLC-MS/MS and application to pharmacokinetic study after oral administration of Gelsemium elegans Benth extract. Biomed. Chromatogr., 2018, 32e4201
[21]
Liu, Y.C.; Lin, L.; Cheng, P.; Sun, Z.L.; Wu, Y.; Liu, Z.Y. Fingerprint analysis of Gelsemium elegans by HPLC followed by the targeted identification of chemical constituents using HPLC coupled with quadrupole-time-of-flight mass spectrometry. Fitoterapia, 2017, 121, 94-105.
[22]
Lai, C.K.; Chan, Y.W. Confirmation of Gelsemium poisoning by targeted analysis of toxic Gelsemium alkaloids in urine. J. Anal. Toxicol., 2009, 33, 56-61.
[23]
Su, Y.P.; Shen, J.; Xu, Y.; Zheng, M.; Yu, C.X. Preparative separation of alkaloids from Gelsemium elegans Benth. using pH-zone-refining counter-current chromatography. J. Chromatogr. A, 2011, 1218, 3695-3698.
[24]
Rujjanawate, C.; Kanjanapothi, D.; Panthong, A. Pharmacological effect and toxicity of alkaloids from Gelsemium elegans Benth. J. Ethnopharmacol., 2003, 89, 91-95.
[25]
Xu, Y.; Qiu, H.Q.; Shen, J.; Zhuang, W.X.; Zhuang, J.Q.; Zheng, G.Y. al., e. No morphine-like drug dependence potential of koumine. J. Fujian. Med. Univ., 2013, 47, 210-213.
[26]
Chen, S.S.; Chen, Y.H.; Xu, Z.Q. Clinical characteritics of Gelsemium poisoning and its treament. Chin. Crit. Care Med., 2006, 26, 298-300.
[27]
Xie, L.J.; Han, X.F. Mechanism, clinical characteristics and management of Gelsemium elegans poisoning. J. Adv. Drug. Effect., 2006, 8, 202-204.
[28]
Pan, G.Y. The rescue of eight patients with Gelsemism poisoning. J. Chin. Pharm., 2008, 17, 56-57.

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