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Preclinical pharmacokinetics of M10 after intragastrical administration of M10-H and M10-Na in Wistar rats.
Journal of Chromatography B ( IF 3 ) Pub Date : 2019-11-30 , DOI: 10.1016/j.jchromb.2019.121905
Jiarui Gao 1 , Guifang Dou 2 , Xiaoxia Zhu 2 , Hui Gan 2 , Ruolan Gu 2 , Zhuona Wu 2 , Taoyun Liu 2 , Suxiang Feng 3 , Zhiyun Meng 2
Affiliation  

As a myricetin derivative, M10 is a potent agent of anti-chronic colonic inflammation. It has better activity than myricetin in preventing azoxymethane/dextran sulfate sodium - induced ulcerative colitis. Here, we introduce a sensitive quantification method based on ultra performance liquid chromatography-tandem mass spectrometry for the determination of M10-H and M10-Na in Wistar rat plasma. Samples were treated with L - ascorbic acid and phosphate buffer solution to maintain stability and with acetonitrile to remove the proteins in the plasma. The supernatant was separated with BEH C18 column and eluted with ultrapure water and acetonitrile both containing 0.1% formic acid. The detection was performed by a triple quadrupole mass spectrometer with positive electrospray ionization mode in multiple reactive monitoring. This method was validated for the carryover effect, selectivity, accuracy, precision, matrix effect, stability, and recovery. A linear correlation was established between concentration and response by the calibration curves over 10-2000 ng·mL-1 (r > 0.99). This method was applied to a pharmacokinetic study of intragastrical administration of M10-H and M10-Na in Wistar rats. In addition, the relative bioavailability of M10-H to M10-Na in Wistar rats was 60 ± 19%, calculated by the ratio of area under concentration (AUC) of M10-H to M10-Na after intragastrical administration of a single dose (100 mg·kg-1 for M10-H and M10-Na, respectively) in Wistar rats.

中文翻译:

Wistar大鼠在胃内施用M10-H和M10-Na后M10的临床前药代动力学。

作为杨梅素衍生物,M10是抗慢性结肠炎的有效药物。它在防止乙氧基甲烷/右旋糖酐硫酸钠诱导的溃疡性结肠炎方面具有比杨梅素更好的活性。在这里,我们介绍了一种基于超高效液相色谱-串联质谱的灵敏定量方法,用于测定Wistar大鼠血浆中的M10-H和M10-Na。样品用L-抗坏血酸和磷酸盐缓冲液处理以保持稳定性,并用乙腈去除血浆中的蛋白质。用BEH C18柱分离上清液,并用都含有0.1%甲酸的超纯水和乙腈洗脱。通过具有正电喷雾电离模式的三重四极杆质谱仪在多反应监测中进行检测。验证了该方法的残留效应,选择性,准确性,精密度,基质效应,稳定性和回收率。通过浓度曲线在10-2000 ng·mL-1(r> 0.99)上建立浓度与响应之间的线性关系。该方法用于Wistar大鼠胃内给药M10-H和M10-Na的药代动力学研究。此外,Wistar大鼠中M10-H与M10-Na的相对生物利用度为60±19%,这是通过单剂量胃内给药后M10-H与M10-Na的浓缩面积比(AUC)计算得出的( Wistar大鼠的M10-H和M10-Na分别为100 mg·kg-1。通过浓度曲线在10-2000 ng·mL-1(r> 0.99)上建立浓度与响应之间的线性关系。该方法用于Wistar大鼠胃内给药M10-H和M10-Na的药代动力学研究。此外,Wistar大鼠中M10-H与M10-Na的相对生物利用度为60±19%,这是通过单剂量胃内给药后M10-H与M10-Na的浓缩面积比(AUC)计算得出的( Wistar大鼠的M10-H和M10-Na分别为100 mg·kg-1。通过浓度曲线在10-2000 ng·mL-1(r> 0.99)上建立浓度与响应之间的线性关系。该方法用于Wistar大鼠胃内给药M10-H和M10-Na的药代动力学研究。此外,Wistar大鼠中M10-H与M10-Na的相对生物利用度为60±19%,这是通过单剂量胃内给药后M10-H与M10-Na的浓缩面积比(AUC)计算得出的( Wistar大鼠的M10-H和M10-Na分别为100 mg·kg-1。
更新日期:2019-11-30
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