Pharmacokinetic Study of Four Major Bioactive Components of Liandan Xiaoyan Formula in Ulcerative Colitis and Control Rats Using UPLC-MS/MS.

Pharmacokinetic Study of Four Major Bioactive Components of Liandan Xiaoyan Formula in Ulcerative Colitis and Control Rats Using UPLC-MS/MS.
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UPLC-MS/MS法研究连丹消炎方四种主要活性成分在溃疡性结肠炎大鼠和正常大鼠体内的药代动力学

DOI:
10.3389/fphar.2022.936846
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发表时间:
2022
影响因子:
5.6
通讯作者:
Zhu, Chenchen
Zhu, Chenchen
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Kaihui;Lu, Zenghui;Wang, Qian;Liu, Fangle;Wang, Meiqi;Lin, Chaozhan;Zhu, Chenchen

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连丹消炎方是根据中医理论由两味中草药组成的治疗肠道疾病的经典中药方剂。本研究旨在建立一种快速、稳定、灵敏、可靠的超高效液相色谱-串联质谱联用方法采用超高效液相色谱-串联质谱法(UPLC-MS/MS)同时测定LXF的四种主要生物活性成分(穿心莲内酯,脱氢穿心莲内酯,1-甲氧基羰基-β-咔啉,4-甲氧基-5-羟基-角黄素-6-酮)在大鼠血清中的浓度,并评估LXF在溃疡性结肠炎(UC)和对照大鼠中的药代动力学特征。甲醇沉淀蛋白质后,采用UPLC C18色谱柱,以乙腈和0.1%甲酸组成的移动的流动相梯度洗脱,流速0.4 ml/min,Triple-TOF™ 5600质谱仪,正离子多反应监测(MRM)模式。方法线性关系良好(R2 ≥ 0.9970),日内和日间精密度均小于13.79%,准确度均在± 11.58%以内。该方法已被验证,并应用于比较血清中的分析物的药代动力学曲线的葡聚糖硫酸钠(DSS)和对照大鼠口服给药LXF后。结果表明,LXF的四种主要生物活性成分在两组口服后均迅速吸收,UC组的暴露水平较高。这些活性成分的药动学特性之间的关系为LXF的临床应用提供了必要的科学依据。
Liandan Xiaoyan Formula (LXF), a classic Traditional Chinese medicine (TCM) formula, is composed of two Chinese herbal medicines for treating bowel disease under the TCM theory. This study aimed to develop a rapid, stable, sensitive, and reliable method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to simultaneously determine four major bioactive components of LXF (andrographolide, dehydroandrographolide, 1-methoxicabony-β-carboline, 4-methoxy-5-hydroxy-canthin-6-one) in rat serum and evaluate the pharmacokinetic characteristics of LXF in ulcerative colitis (UC) and control rats. 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 0.4 ml/min. Detection was performed on Triple-TOF™ 5600 mass spectrometry set at the positive ionization and multiple reaction monitoring (MRM) mode. The validated method showed good linearity (R 2 ≥ 0.9970), the intra- and inter-day accuracy were within ±11.58%, whereas the intra- and inter-day precision were less than 13.79%. This method was validated and applied to compare the pharmacokinetic profiles of the analytes in serum of UC induced by dextran sulphate sodium (DSS) and control rats after oral administration of LXF. The results showed that four major bioactive components of LXF were quickly absorbed after oral administration in both groups, with higher exposure levels in the UC group. This relationship between the active ingredients’ pharmacokinetic properties provided essential scientific information for applying LXF in clinical.
DOI: 10.1136/bmjopen-2020-037443
发表时间: 2020-10-01
期刊: BMJ open
影响因子: 2.9
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DOI: 10.1093/ecco-jcc/jjy215
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影响因子: 8
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