Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry

doi:10.1016/j.jpba.2010.01.040

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	Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry
	Deng, Pan 2; Chen, Xiaoyan2 ; Zhang, Guodong 1; Zhong, Dafang2
刊名	JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
	2010-08-01
卷号	52 期号:4 页码:571-579
关键词	Phosphorothioate oligonucleotide Ion-pair reversed phase Liquid chromatography-tandem mass spectrometry Metabolite Pharmacokinetics
ISSN号	0731-7085
DOI	10.1016/j.jpba.2010.01.040
文献子类	Article
英文摘要	An ion-pair reversed phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantification of a phosphorothioate oligonucleotide (PS-OGN) PF-ODN and its metabolites 5'N-1/3'N-1, 5'N-2 and 5'N-3 in rat plasma. Plasma samples were prepared with an initial phenol/dichloromethane liquid-liquid extraction followed by a solid phase extraction. Chromatographic separation was performed with a gradient system on a Phenomenex Gemini C-18 column using hexafluoro-2-propanol/triethylamine buffer and methanol as the mobile phase at a flow rate of 0.5 mL/min. Except for 5'N-1 and 3'N-1, which were coeluted and could not be differentiated by mass spectrometer, the other analytes were separated chromatographically and mass spectrometrically. The detection was carried out in multiple reaction monitoring (MRM) mode using a negative electrospray ionization (ESI) interface. The lower limit of quantification (LLOQ) achieved was 4.0 ng/mL for PF-ODN and its four metabolites with acceptable precision and accuracy. Inter-day and intra-clay RSD for three quality control (QC) levels across validation runs were less than 12.0% and the accuracy ranged from -9.6% to 6.0% for the analytes. This validated LC-MS/MS method was applied to a preliminary pharmacokinetic study of PF-ODN in rats. (C) 2010 Elsevier B.V. All rights reserved.
资助项目	Pfizer Global Research and Development[00000000]
WOS关键词	INTERFERING RNA DUPLEX ; ANTISENSE OLIGONUCLEOTIDE ; PHOSPHOROTHIOATE OLIGONUCLEOTIDE ; THERAPEUTIC OLIGONUCLEOTIDES ; PLASMA ; QUANTIFICATION ; IDENTIFICATION ; RAFAON ; MOUSE ; ACIDS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000276057300019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278819]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang
作者单位	1.Pfizer Inc, PGRD, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Deng, Pan,Chen, Xiaoyan,Zhang, Guodong,et al. Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2010,52(4):571-579.
APA	Deng, Pan,Chen, Xiaoyan,Zhang, Guodong,&Zhong, Dafang.(2010).Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,52(4),571-579.
MLA	Deng, Pan,et al."Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 52.4(2010):571-579.