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Simultaneous determination of cucurbitacin B and cucurbitacin E in rat plasma by UHPLC-MS/MS: A pharmacokinetics study after oral administration of cucurbitacin tablets
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2017-09-18 , DOI: 10.1016/j.jchromb.2017.09.024
Zhibin Wang , Wenbo Zhu , Mingjie Gao , Chengcui Wu , Chunjuan Yang , Jing Yang , Gaosong Wu , Bingyou Yang , Haixue Kuang

Cucurbitacin B (CuB) and cucurbitacin E (CuE) are tetracyclic triterpene compounds from Cucurbitaceae, and the main bioactive compounds of cucurbitacins tablets that used to treatment of chronic hepatitis. Pharmacological research has been very comprehensive, and there are few studies on pharmacokinetics, especially about CuE. An Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method with high selectivity, simplicity and sensitivity has been used for quantitative analysis of Cucurbitacin B (CuB) and cucurbitacin E (CuE). Plasma samples were pretreatment by Liquid-liquid extraction (LLE) method with dichloromethane. The chromatographic separation was achieved on a C18 column (Agilent Eclipse Plus, 1.8 μm, 50 × 2.1 mm) using gradient elution with water – methanol at a flow rate of 0.3 mL/min and the column temperature was set at 30 °C. The method was validated according to FDA guidelines. Lower limit of quantification (LLOQ) was 1.60 ng/mL for CuB and 1.58 ng/mL for CuE. Correlation coefficients of CuB and CuE were more than 0.99 in rat plasma. All values of intra-day and inter-day precision (RSD%) were not exceeded 15%, the accuracy (RE%) were within −5.57 to 5.20% for CuB and −3.33 to 7.37% for CuE. The mean extraction recoveries were more than 80%. Pharmacokinetic parameters were also evaluated by UHPLC-MS/MS method. The results suggestion that this method was successfully applied to pharmacokinetic study of CuB and CuE in rat plasma after oral administration cucurbitacin tablets.



中文翻译:

通过UHPLC-MS / MS同时测定大鼠血浆中葫芦素B和葫芦素E:葫芦素片口服后的药代动力学研究

葫芦素B(CuB)和葫芦素E(CuE)是来自葫芦科的四环三萜类化合物,是用于治疗慢性肝炎的葫芦素片的主要生物活性化合物。药理学研究非常全面,关于药代动力学的研究很少,特别是关于CuE的研究。具有高选择性,简便性和灵敏度的超高效液相色谱-串联质谱(UHPLC-MS / MS)方法已用于葫芦素B(CuB)和葫芦素E(CuE)的定量分析。血浆样品采用二氯甲烷通过液-液萃取(LLE)方法进行预处理。色谱分离是在C 18上完成的色谱柱(Agilent Eclipse Plus,1.8μm,50×2.1 mm),使用水-甲醇以0.3 mL / min的流速进行梯度洗脱,色谱柱温度设置为30°C。该方法已根据FDA指南进行了验证。CuB的定量下限(LLOQ)为1.60 ng / mL,CuE的定量下限(LLOQ)为1.58 ng / mL。大鼠血浆中CuB和CuE的相关系数均大于0.99。日内和日间精度(RSD%)的所有值均不超过15%,CuB的精度(RE%)在-5.57至5.20%之内,CuE的精度在(3.33%至7.37%)之内。平均提取回收率超过80%。还通过UHPLC-MS / MS方法评估了药代动力学参数。结果提示,该方法成功应用于口服葫芦素片后大鼠血浆中CuB和CuE的药代动力学研究。

更新日期:2017-09-18
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