Pharmacokinetic Study of Multiple Components of Gelsemium elegans in Goats by Ultra-Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry

Pharmacokinetic Study of Multiple Components of Gelsemium elegans in Goats by Ultra-Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry
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DOI:
10.1093/jat/bkz100
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发表时间:
2020-05-01
影响因子:
2.5
通讯作者:
Liu, Zhao-Ying
Liu, Zhao-Ying
中科院分区:
医学3区
文献类型:
--
作者:
Cao, Jun-Jie;Yang, Kun;Liu, Zhao-Ying

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钩吻(Gelsemium elegans(G. elegans)已被用于传统中药中。这种植物对人类有很高的毒性,但在兽医诊所可以促进猪和山羊的生长。它是一种非常复杂的混合物,含有数十种或数百种不同的成分。因此,G.由于缺乏成分的真实标准,秀丽线虫是一个重大挑战。本研究的目的是研究单剂量口服G. elegans在山羊使用一个敏感的超高效液相色谱串联质谱法同时半定量多种生物碱没有标准。在专属性、LOD、LOQ、线性、准确度、精密度和基质效应方面对该方法进行了验证。为了验证全球的药代动力学特征,从半定量分析三个真实的化合物(钩吻素,钩吻素和humantenmine)获得的结果进行了比较,从我们最近发表的方法的绝对定量。结果表明,两种方法的分析结果基本一致,3种生物碱的Tmax、T-1/2和MRT 0-t值基本一致。此外,归一化后的C-max和AUC(0-t)值与真实的值接近,表明该半定量方法可用于多组分的药动学研究。测定了23种G.获得山羊中的秀丽隐杆线虫生物碱。结果表明,钩吻生物碱是预测和解释钩吻药效和毒性的主要活性成分。优美的
Gelsemium elegans (G. elegans) has been used in traditional Chinese medicine. This plant is highly toxic to humans, but can promote the growth of pigs and goats in the veterinary clinic. It is a very complex mixture containing tens or hundreds of different components. Therefore, multiple-component pharmacokinetic studies of G. elegans are a major challenge due to the lack of authentic standards of the components. The purpose of this study was to investigate the plasma pharmacokinetics of multiple components after a single oral dose of G. elegans in goat using a sensitive ultra-performance liquid chromatography coupled to tandem mass spectrometry method for the simultaneous semiquantification of multiple alkaloids without standards. The method was validated in terms of the specificity, LOD, LOQ, linearity, accuracy, precision and matrix effects. To validate the global pharmacokinetic characteristics, the results obtained from the semiquantitative analysis of three authentic compounds (gelsemine, koumine and humantenmine) were compared with the absolute quantification from our recently published method. The results showed that the two methods had similar analytical results, and the obtained values of T-max, T-1/2 and MRT0-t of the three alkaloids were similar between the two methods. In addition, the values of C-max and AUC(0-t) of the three alkaloids after normalization were close to the real values, which indicated that this semiquantitative method could be used in the pharmacokinetic study of multiplecomponents. Then the pharmacokinetic parameters of 23 other G. elegans alkaloids in goats were obtained. The results suggested that the gelsedine-type alkaloids were the major active ingredients that predict and explain the efficacy and toxicity of G. elegans.