Chen Tao, Chen Zhonghua, Zhang Suxing, Zhang Kezhi, Wang Laiyou
Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory against Metabolic Diseases, Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou, 510006 People's Republic of China.
Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 People's Republic of China.
Springerplus. 2015 Oct 29;4:652. doi: 10.1186/s40064-015-1446-0. eCollection 2015.
Hetrombopag as the derivative of ethylidene hydrazine carboxamide was recently developed into a novel patented non-peptide thrombopoietin mimetic and thrombopoietin receptor agonist to treat idiopathic thrombocytopenic purpura. To study the pharmacokinetics of hetrombopag, a highly sensitive, rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of hetrombopag in rat plasma. After protein precipitation extraction, the chromatography separation of analyte and internal standard named eltrombopag as an marketed analog of hetrombopag was performed on an Synergi Polar-RP column at the flow rate of 0.5 mL/min, and the determination was conducted on an API4000 triple quadrupole mass spectrometry in the multiple reaction monitoring mode using the respective M+H ions m/z 459.2 → 200.9 for hetrombopag and m/z 443.2 → 229.0 for IS. The lower limit of quantification was established to be 1 ng/mL, and the linear scope of standard curve was 1-1000 ng/mL. Both the precision (RSD%) and accuracy (RE%) were within the acceptable criterion of below 15 %. The validated method was successfully applied to quantify hetrombopag in the rat plasma and investigate the pharmacokinetics.
海曲泊帕作为亚乙基肼甲酰胺的衍生物，最近被开发成为一种新型的专利非肽类血小板生成素模拟物和血小板生成素受体激动剂，用于治疗特发性血小板减少性紫癜。为研究海曲泊帕的药代动力学，开发并验证了一种高灵敏度、快速且可靠的液相色谱-串联质谱（LC-MS/MS）方法，用于测定大鼠血浆中的海曲泊帕。经蛋白沉淀提取后，在Synergi Polar-RP柱上以0.5 mL/min的流速对分析物和作为海曲泊帕市售类似物的内标艾曲泊帕进行色谱分离，并在API4000三重四极杆质谱仪上采用多反应监测模式进行测定，海曲泊帕的M+H离子m/z 459.2→200.9，内标的M+H离子m/z 443.2→229.0。定量下限设定为1 ng/mL，标准曲线的线性范围为1 - 1000 ng/mL。精密度（RSD%）和准确度（RE%）均在可接受标准范围内，即低于15%。该验证方法成功应用于定量大鼠血浆中的海曲泊帕并研究其药代动力学。
