Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry

doi:10.1016/j.jchromb.2019.05.018

	Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry
	Hou, Xiangyu 1,2; Dai, Xiaojian 1; Yang, Yong 1; Zhang, Yifan 1; Zhong, Dafang 1,2; Chen, Xiaoyan 1,2
刊名	JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
	2019-08-01
卷号	1122 页码:58-63
关键词	Imrecoxib Imrecoxib active metabolites Pharmacokinetics LC-MS/MS Human Moderate impairment
ISSN号	1570-0232
DOI	10.1016/j.jchromb.2019.05.018
通讯作者	Chen, Xiaoyan(xychen@simm.ac.cn)
英文摘要	Imrecoxib is a specific inhibitor of cyclooxygenase-2. Its hydroxymethyl (Ml) and carboxylic acid (M2) metabolites are the major circulating components in human plasma. It has been demonstrated that the anti-inflammatory activities of M1 and M2 are both equal to the parent drug. In the current study, a highly sensitive and rapid method was established and validated for the determination of imrecoxib, M1 and M2 in human plasma via liquid chromatography-tandem mass spectrometry technique. To our knowledge, this is the first study that simultaneously analyzed imrecoxib and its two active metabolites following a rapid protein-precipitation clean-up. Imrecoxib and its metabolites were separated on a reversed-C18 column (3.5 m; 100 x 4.6 mm), and the mobile phase was optimized as 5 mM ammonium acetate: acetonitrile: formic acid (35: 65: 0.1, v/v/v), based on the pKa values of analytes. Mass spectrometric detection was conducted in a positive multiple reaction monitoring mode. The m/z transitions of imrecoxib (370.2 -> 278.2), M1 (386.2 -> 278.2) and M2 (400.2 -> 236.2) were selected for an effective balance between sensitivity and selectivity. An excellent linearity was demonstrated over the concentration ranges of 0.100-40.0, 0.200-80.0 and 2.00-800 ng/mL for imrecoxib, M1 and M2, respectively. The method validation was carried out in agreement with the FDA guidance. Furthermore, the pharmacokinetic properties of imrecoxib and its two active metabolites were characterized in patients with moderate hepatic impairment, by using the developed and validated method.
资助项目	National Natural Science Foundation of China[81573500] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA 12050306]
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000474499000006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289306]
专题	中国科学院上海药物研究所
通讯作者	Chen, Xiaoyan
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Hou, Xiangyu,Dai, Xiaojian,Yang, Yong,et al. Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2019,1122:58-63.
APA	Hou, Xiangyu,Dai, Xiaojian,Yang, Yong,Zhang, Yifan,Zhong, Dafang,&Chen, Xiaoyan.(2019).Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1122,58-63.
MLA	Hou, Xiangyu,et al."Simultaneous determination of imrecoxib and its two active metabolites in plasma of hepatic impairment patients by liquid chromatography-tandem mass spectrometry".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1122(2019):58-63.