Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study.

Development and Validation of a HPLC-ESI-MS/MS Method for Simultaneous Quantification of Fourteen Alkaloids in Mouse Plasma after Oral Administration of the Extract of Corydalis yanhusuo Tuber: Application to Pharmacokinetic Study.
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口服延胡索块茎提取物后同时定量小鼠血浆中 14 种生物碱的 HPLC-ESI-MS/MS 方法的开发和验证:在药代动力学研究中的应用

DOI:
10.3390/molecules23040714
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发表时间:
2018-03-21
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Zhou H
Zhou H
中科院分区:
其他
文献类型:
--
作者:
Du W;Jin L;Li L;Wang W;Zeng S;Jiang H;Zhou H

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延胡索是我国著名的传统中药,具有镇痛、抗肿瘤、抗菌、抗炎、抗抑郁等药理作用。虽然目前有多种方法可用于生物活性成分生物碱的分析和检测,但迄今为止,只有少数突出的生物碱可被定量,综合生物碱口服后的体内外变化仍知之甚少。本研究首次建立了一种简便、灵敏的高效液相色谱-电喷雾-串联质谱(HPLC-ESI-MS/MS)方法,用于对川滇贝母提取物中的综合生物碱进行定量分析。以氯化两面针碱为内标,测定了小鼠血浆中延胡索的含量。结果表明,至少14种生物碱,包括阿朴啡(oxoglaucine),原阿片碱(protopine),五个三级生物碱(coronaline,tetrahydroberberberine,tetrahydropalmatine,tetrahydrocolumbamine,和tetrahydrocoptisine)和七个四级生物碱(columbamine,palmatine,berberine,epiberberine,coptisine,jatrorrhizine,和dehydrocoronaline)可以很好地定量同时在小鼠血浆中。定量下限大于或等于0.67 ng/mL,平均基质效应范围为96.4%-114.3%。质控样品的平均提取回收率大于71.40%,精密度和准确度均在可接受范围内。所有分析物在不同储存条件下均显示稳定。并将建立的方法应用于延胡索提取物在小鼠体内的药代动力学研究。据我们所知,这是第一个全面和同时分析的文献。小鼠血浆中延胡索的含量。这是有效的和有用的综合药代动力学和代谢组学分析后,这些复杂的生物碱给药。
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.
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