HPLC-MS/MS analysis of primary alkaloids in rat plasma after oral administration of "Nux vomica - Glycyrrhiza glabra decoction": A pharmacokinetic study.

Autor: Guo Y; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: guoyuyan622@163.com., Meng Z; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: m1121849121@163.com., Gu Y; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: yuanwas@163.com., Li W; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: liweinan@hljucm.net., Sun S; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: 309642421@qq.com., Wang Q; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 511400, China. Electronic address: qhwang668@sina.com., Kuang H; Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, 150040, China. Electronic address: hxkuang15@hotmail.com.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2022 Nov 15; Vol. 298, pp. 115588. Date of Electronic Publication: 2022 Aug 02.
DOI: 10.1016/j.jep.2022.115588
Abstrakt: Ethnopharmacological Relevance: Decoction is the most common form of administering traditional Chinese medicine (TCM). During the preparation of decoction, the high temperature and complex chemical environment result in the formation of complex and multiple phases. The differences in drug components in different phases induce gastrointestinal absorption and physiological response. Nux vomica (Strychnos nux-vomica L) is a typical toxic TCM used in China, with remarkable pharmacological activity. In order to reduce its toxicity, nux vomica (NV) is often decocted with Glycyrrhiza glabra (GG) in clinic, and the detoxification mechanism has always been the focus of research interest. Most studies investigated the compatibility of NV-GG, but the in vivo behavior of individual constituents based on phase state has yet to be elucidated.
Aim of the Study: To investigate the pharmacokinetic behavior of typical toxic components in different phase states of "NV-GG decoction" in rat plasma.
Materials and Methods: The sediment, suspension, colloid and true solution of "NV-GG decoction" was obtained via physical methods. The main components in different phase states were analyzed via reliable UFLC-Q-TOF-MS high-resolution mass spectrometry. A rapid and accurate HPLC-qqq-MS/MS method was established and validated for accurate determination of brucine and strychnine levels in plasma, followed by pharmacokinetic evaluation of different phase states of "NV-GG decoction" in rats. Kinetex F5 100A (50 mm × 3.0 mm, 2.6 μm) column was used for chromatographic separation. Aqueous solution containing acetonitrile and 0.1% formic acid was used as the mobile phase, followed by gradient elution at 0.4 mL/min. Mass spectra were detected by electrospray ionization (ESI) multiple reaction monitoring (MRM) in positive ion mode.
Results: Fifteen different alkaloids were detected in different phase states of "NV-GG decoction". Strychnine and brucine, which are toxic components with high content, were selected for quantitative analysis. The established UPLC-qqq-MS/MS method is accurate and reliable with a good linearity (R 2  > 0.99) in the respective concentration range, satisfying the quantitative requirements. The pharmacokinetic parameters of different phase states of rats differed significantly after gavage. The deposition phase was the most prominent. The index components showed higher C max , AUC 0 and T max , while the T 1/2 , MRT, V/F and CL/F were the smallest, with a relatively slow plasma clearance rate in rats. The true solution group showed the lowest T max and the fastest absorption.
Conclusion: This method has been successfully utilized to study the pharmacokinetics of different phase states of "NV-GG decoction". Among the four phases, the deposition phase contributed to a large proportion of the in vivo kinetic behavior similar to that of sustained-release preparations, with slow absorption of toxic components and prolonged peak time. The pharmacokinetic parameters and plasma concentration-time curves of each phase can be used to study toxicity reduction of NV-GG and increase its biocompatibility.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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