Validated LC-MS/MS method for determination of YH-8, a novel PKnB inhibitor, in rat plasma and its application to pharmacokinetic study

文献类型： 外文期刊

第一作者： Zhai, Qianqian

作者： Zhai, Qianqian;Pang, Jing;Li, Guoqing;Li, Congran;Yang, Xinyi;Yu, Liyan;Wang, Yucheng;You, Xuefu;Zhai, Qianqian;Pang, Jing;Li, Guoqing;Li, Congran;Yang, Xinyi;Yu, Liyan;Wang, Yucheng;You, Xuefu;Zhai, Qianqian;Li, Jian

作者机构：

关键词： YH-8;LC-MS/MS;Pharmacokinetics;Rat plasma;Method validation

期刊名称：ACTA PHARMACEUTICA SINICA B （ 影响因子：11.413； 五年影响因子：10.745 ）

ISSN： 2211-3835

年卷期： 2015 年 5 卷 5 期

页码：

收录情况： SCI

摘要： (E)-Methyl-4-aryl-4-oxabut-2-enoa (YH-8) is a novel PKriB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography tandem mass spectrometric (liC:MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasm for the lust Curie. Samples were pre-treated using a liquid liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good line:Hit); over the range of 1-500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. lntra- and inter-day precision of YR-8 assay in rat plasma samples were 2.0c7c-6.8%, with accuracy of the method being 100.69c.70-106.1.8%. Stability test showed that Mien spiked into rat plasma. YH-8 was stable for 12 h at room temperature, for up to 15 days at -70 degrees C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the phannacArinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg. (c) 2015 Chinese Pharmaceutical Association and Institute of Materia Medial., Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

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