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Pharmacokinetic and bioavailability study of kurarinone in dog plasma by UHPLC-MS/MS.
Biomedical Chromatography ( IF 1.8 ) Pub Date : 2020-07-13 , DOI: 10.1002/bmc.4945
Yiqian Huang 1 , Huashan Lin 2 , Yaping Chen 3 , Xiaosong Huang 1
Affiliation  

Kurarinone, a natural prenylated flavonone isolated from Sophora flavescens, has been exhibited various activities. This study aimed to establish a simple and sensitive ultra‐high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for determining kurarinone in dog plasma. Acetonitrile‐mediated precipitation was applied for sample pretreatment. Chromatographic separation was achieved on a Waters ACQUITY HSS T3 (100 × 2.1 mm, i. d., 1.8 μm) column with gradient elution using water containing 0.1% formic acid and acetonitrile as mobile phase. Quantitation was performed using an electrospray ionization source in negative multiple reaction monitoring mode. The linearity of this method was over the concentration range 0.1–500 ng/mL with the lowest limit of quantification (LLOQ) of 0.1 ng/mL. The intra‐ and inter‐day precision was less than 10.51% and the accuracy ranged from 94.85% to 97.72%, respectively. The extraction recovery of kurarinone in dog plasma was more than 82.37% and no significant matrix effect was observed. The analyte was stable under tested storage conditions. The validated method was further successfully applied to a preclinical pharmacokinetic study of kurarinone in dog after a single intravenous (2 mg/kg) and oral (20 mg/kg) administration. The results revealed that kurarinone was rapidly absorbed into plasma with good bioavailability (38.19%) and low clearance.

中文翻译:

通过UHPLC-MS / MS研究可乐利酮在狗血浆中的药代动力学和生物利用度。

苦参酮(Kurarinone),一种天然苦参黄酮,从苦参中分离,已展出各种活动。本研究旨在建立一种简单灵敏的高效液相色谱-串联质谱法(UHPLC-MS / MS)测定狗血浆中的可乐酮。乙腈介导的沉淀用于样品预处理。在Waters ACQUITY HSS T3(100×2.1 mm,id,1.8μm)色谱柱上进行色谱分离,使用含有0.1%甲酸和乙腈的水作为流动相进行梯度洗脱。使用电喷雾电离源以负多重反应监测模式进行定量。该方法的线性在0.1–500 ng / mL的浓度范围内,最低定量限(LLOQ)为0.1 ng / mL。日内和日间准确度均低于10.51%,准确度介于94.85%至97.72%之间,分别。狗血浆中可乐酮的提取回收率超过82.37%,未见明显的基质效应。分析物在测试的储存条件下稳定。经过验证的方法可进一步成功地应用于狗中可乐那酮的单次静脉内(2 mg / kg)和口服(20 mg / kg)给药的临床前药代动力学研究。结果表明,可乐酮能被血浆快速吸收,具有良好的生物利用度(38.19%)和低清除率。经过验证的方法可进一步成功地应用于狗中可乐那酮的单次静脉内(2 mg / kg)和口服(20 mg / kg)给药的临床前药代动力学研究。结果表明,可乐酮能被血浆快速吸收,具有良好的生物利用度(38.19%)和低清除率。经过验证的方法可进一步成功地应用于狗中可乐那酮的单次静脉内(2 mg / kg)和口服(20 mg / kg)给药的临床前药代动力学研究。结果表明,可乐酮能被血浆快速吸收,具有良好的生物利用度(38.19%)和低清除率。
更新日期:2020-07-13
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