Pharmacokinetic study of seven bioactive components of Xiaoyan Lidan Formula in cholestatic and control rats using UPLC-MS/MS.
Pharmacokinetic study of seven bioactive components of Xiaoyan Lidan Formula in cholestatic and control rats using UPLC-MS/MS.
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DOI：
10.1016/j.biopha.2021.111523
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Kaihui Zhang;Meiqi Wang;Yufeng Yao;Tao Huang;Fangle Liu;Chenchen Zhu;Chaozhan Lin
中科院分区：
文献类型：
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作者：
Kaihui Zhang;Meiqi Wang;Yufeng Yao;Tao Huang;Fangle Liu;Chenchen Zhu;Chaozhan Lin
以磺胺甲恶唑为内标，建立了快速、灵敏、可靠的超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定消炎利胆方大鼠血浆中主要生物活性成分的方法。7种主要生物活性成分分别为穿心莲内酯、脱水穿心莲内酯、烯醇胺、1-甲氧基-β-卡宾、4，5-二甲氧基-卡宁-6-酮、4-甲氧基-5-羟基-卡宁-6-酮和1-羟甲基-β-卡宾。采用UPLC C18色谱柱，以乙腈-0.1%甲酸为流动相，流速为0.7 mg/m in。检测采用TSQ量子质谱仪，正/负电离和多反应监测(MRM)模式。日内、日间精密度均小于9.8%，日内、日间精密度均在±13.4%以内。将该方法用于α-异硫氰酸酯(ANIT)诱导的胆汁淤积大鼠和正常大鼠口服XYLDF后的血清药代动力学比较。结果表明，模型组和对照组的药代动力学性质有显著差异，从而为更好地了解消炎利胆方的作用机制提供了必要的科学信息，为其临床应用提供了参考。
A rapid, sensitive, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed to simultaneously determine the major bioactive components of Xiaoyan Lidan Formula (XYLDF) in rat plasma, using sulfamethoxazole as the internal standard (IS). The seven major bioactive components are andrographolide, dehydroandrographolide, enmein, 1-methoxicabony-β-carboline, 4,5-dimethoxy-canthin-6-one, 4-methoxy-5-hydroxy-canthin-6-one, and 1-hydroxymethyl-β-carboline. After pretreating by protein precipitation with methanol, separation was performed on a UPLC C18 column using gradient elution with a mobile phase consisting of acetonitrile and 0.1% formic acid at a flowing rate of 0.7 mL/min. Detection was performed on TSQ Quantum mass spectrometry set at the positive/negative ionization and multiple reaction monitoring (MRM) mode. The intra- and inter-day precision were less than 9.8%, whereas the intra- and inter-day accuracy were within ± 13.4%. The method was validated and applied to compare the pharmacokinetic profiles of the analytes in serum of Alpha-naphthylisothiocyanate (ANIT)-induced cholestasis and control rats after oral administration of XYLDF. The results showed remarkable differences in pharmacokinetic properties of the analytes between cholestatic (model) and control groups, thereby providing essential scientific information for better understanding of mechanism of XYLDF and a reference for its clinical applications.