Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood

doi:10.1016/j.jchromb.2014.01.017

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	Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood
	Yu, Yang 1,2; Zhan, Yan2 ; Chen, Xiaoyan2 ; Zhang, Yifan2 ; Zhong, Dafang2
刊名	JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
	2014-03-01
卷号	951 页码:62-68
关键词	Sinotecan 7-Hydroxyethyl-camptothecin LC-MS/MS Pharmacokinetics
ISSN号	1570-0232
DOI	10.1016/j.jchromb.2014.01.017
文献子类	Article
英文摘要	Sinotecan is a camptothecin analog, currently under clinical testing as an antitumor medication. We developed and validated a rapid, specific and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of sinotecan and its active metabolite, 7-hydroxyethyl-camptothecin (7-HEC), in human blood. Aliquots (200 mu L) of heparinized blood samples were processed by deproteinization with 400 mu L. acetonitrile each. Chromatographic analyte separation used an Agilent Zorbax SB C-8 column (4.6 mm x 150 mm, 5 mu m) and methanol/10 mM ammonium acetate/formic acid (70/30/0.14, v/v/v) as mobile phase, at a flow rate of 0.60 mL/min. A Thermo Finnigan TSQ Quantum Ultra tandem mass spectrometer was operated in multiple-reaction monitoring mode. The precursor-to-product ion transitions m/z 493 -> m/z (331+375) for sinotecan, m/z 393 m/z (233+261) for 7-HEC, and m/z 396 -> m/z 352 for d(3)-SN38 (IS) were used for quantification. The method was validated for 1.0-500 ng/mL for sinotecan and 0.5-250 ng/mL for 7-HEC using 200111 of blood sample. Total time for each chromatograph was similar to 6.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<13.8% and the accuracy values ranged from -5.3% to 2.4%. The method was successfully applied to a pharmacokinetic study of sinotecan in cancer patients (C) 2014 Elsevier B.V. All rights reserved.
资助项目	National Natural Science Foundation of China[81173117]
WOS关键词	PERFORMANCE LIQUID-CHROMATOGRAPHY ; TANDEM MASS-SPECTROMETRY ; HUMAN WHOLE-BLOOD ; HUMAN PLASMA ; IRINOTECAN CPT-11 ; FLUORESCENCE DETECTION ; TOPOTECAN ; SN-38 ; LACTONE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000332806100010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277169]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang
作者单位	1.Bethune Int Peace Hosp, Dept Clin Pharm, Shijiazhuang 050082, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Yu, Yang,Zhan, Yan,Chen, Xiaoyan,et al. Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2014,951:62-68.
APA	Yu, Yang,Zhan, Yan,Chen, Xiaoyan,Zhang, Yifan,&Zhong, Dafang.(2014).Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,951,62-68.
MLA	Yu, Yang,et al."Development and validation of a sensitive LC-MS/MS method for simultaneous quantification of sinotecan and its active metabolite in human blood".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 951(2014):62-68.