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基于液相色谱-质谱联用的新型过氧化物酶体增殖物激活受体γ激动剂KR-62980定性定量分析方法

LC-MS-based method for the qualitative and quantitative analysis of the novel PPARγ agonist KR-62980.

作者信息

Kim Min-Sun, Bae Myung Ae

机构信息

Drug Discovery Platform Technology Team, Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejon, South Korea.

出版信息

Methods Mol Biol. 2013;952:313-23. doi: 10.1007/978-1-62703-155-4_23.

Abstract

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for a novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, KR-62980, in rat plasma. It involves liquid-liquid extraction (LLE) followed by HPLC separation and electrospray ionization tandem mass spectrometry. The linear ranges of the assay were 0.01-10 μg/mL with a correlation coefficient (R (2)) greater than 0.99 and the lower limit of quantification was 0.01 μg/mL. The average recovery was 90.1 and 98.4% from rat plasma for KR-62980 and imipramine, respectively. The coefficients of variation of intra- and inter-assay were 1.2-10.6% and the relative error was 0.8-13.2%. The method was validated and successfully applied to the pharmacokinetic study of KR-62980 in rat.

摘要

建立了一种灵敏的液相色谱/串联质谱(LC/MS/MS)方法,用于测定大鼠血浆中新型过氧化物酶体增殖物激活受体γ(PPARγ)激动剂KR-62980。该方法包括液-液萃取(LLE),随后进行高效液相色谱分离和电喷雾电离串联质谱分析。该测定方法的线性范围为0.01-10μg/mL,相关系数(R(2))大于0.99,定量下限为0.01μg/mL。KR-62980和丙咪嗪从大鼠血浆中的平均回收率分别为90.1%和98.4%。批内和批间变异系数分别为1.2-10.6%,相对误差为0.8-13.2%。该方法经过验证,并成功应用于KR-62980在大鼠体内的药代动力学研究。

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