Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma

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	Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma
	Liu Dongqin 2; Yu Jinghua 2; Zhang Yifan2 ; Zhong Dafang2 ; He Ling 1; Chen Xiaoyan2
刊名	Acta Pharmaceutica Sinica
	2015
卷号	50 期号:3 页码:348-354
关键词	LC-MS/MS stable isotope labeled internal standard LC-MS/MS ivabradine N-demethylivabradine
ISSN号	0513-4870
其他题名	稳定同位素内标对人血浆样品中伊伐布雷定和 N-去甲基伊伐布雷定测定的影响
文献子类	Article
英文摘要	This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm * 4.6 mm, 5 mum) column using a mobile phase of methanol and 5 mmol·L~(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3]~+ on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng·mL~(-1) for ivabradine, and 0.050 0 to 20.0 ng·mL~(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:5360090
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/269294]
专题	上海药物代谢研究中心
通讯作者	Chen Xiaoyan
作者单位	1.College of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, China. 2.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.;
推荐引用方式 GB/T 7714	Liu Dongqin,Yu Jinghua,Zhang Yifan,et al. Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma[J]. Acta Pharmaceutica Sinica,2015,50(3):348-354.
APA	Liu Dongqin,Yu Jinghua,Zhang Yifan,Zhong Dafang,He Ling,&Chen Xiaoyan.(2015).Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma.Acta Pharmaceutica Sinica,50(3),348-354.
MLA	Liu Dongqin,et al."Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma".Acta Pharmaceutica Sinica 50.3(2015):348-354.