Abstract
The tuber of Corydalis yanhusuo is a famous traditional Chinese medicine and found to have potent pharmacological effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Although there are several methods to be developed for the analysis and detection of the bioactive ingredients’ alkaloids, so far, only few prominent alkaloids could be quantified, and in vitro and in vivo changes of comprehensive alkaloids after oral administration are still little known. In this study, we first developed a simple and sensitive high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to quantify the comprehensive alkaloids of extracts of C. yanhusuo in mouse plasma, using nitidine chloride as an internal standard. As results, at least fourteen alkaloids, including an aporphine (oxoglaucine), a protopine (protopine), five tertiary alkaloids (corydaline, tetrahydroberberine, tetrahydropalmatine, tetrahydrocolumbamine, and tetrahydrocoptisine) and seven quaternary alkaloids (columbamine, palmatine, berberine, epiberberine, coptisine, jatrorrhizine, and dehydrocorydaline) could be well quantified simultaneously in mouse plasma. The lower limits of quantification were greater than, or equal to, 0.67 ng/mL, and the average matrix effects ranged from 96.4% to 114.3%. The mean extraction recoveries of quality control samples were over 71.40%, and the precision and accuracy were within the acceptable limits. All the analytes were shown to be stable under different storage conditions. Then the established method was successfully applied to investigate the pharmacokinetics of these alkaloids after oral administration of the extract of Corydalis yanhusuo in mice. To the best of our knowledge, this is the first document to report the comprehensive and simultaneous analyses of alkaloids of C. yanhusuo in mouse plasma. It was efficient and useful for comprehensive pharmacokinetic and metabolomic analyses of these complex alkaloids after drug administration.
Highlights
The dried tuber of Corydalis yanhusuo W
We applied the developed method to the pharmacokinetic study of fourteen alkaloids after oral administration of Corydalis yanhusuo extract in mice
We found that the extraction recoveries of tertiary alkaloids were high with a low level of endogenous interference using LLE for sample preparation in mouse plasma, whereas the extraction recoveries of certain quaternary alkaloids, such as columbamine, berberine, palmatine, and dehydrocorydaline, were less than 50% no matter how the pH value was regulated
Summary
The dried tuber of Corydalis yanhusuo W. T. Wang (Corydalis Rhizoma, or Yuanhu in Chinese) is a famous traditional Chinese medicine (TCM) and widely used for blood activation, moving ‘Qi’. It is well known that the main active ingredients of the extract of C. yanhusuo are the alkaloids, which possess potent pharmacological. Molecules 2018, 23, 714 effects, such as antinociceptive, antitumor, antibacterial, anti-inflammatory, and anti-depressive activities. Tetrahydropalmatine, corydaline, and protopine could enter the central nervous system through the blood-brain barrier, and play the role of analgesic, sedative hypnotic, and anxiolytic effects [1,2,3,4]. Oxoglaucine, berberrabine, berberine, coptisine, palmatine, columbamine, and jatrorrhizine were reported to have antitumor activity [5,6,7], while berberine, palmatine and epiberberine were found to have antibacterial activity [8,9]. Tetrahydropalmatine, palmatine, berberine, dehydrocorydaline, tetrahydroberberine, and tetrahydrocolumbamine have cardioprotective effects [10,11,12]
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