Bioanalysis of an oligonucleotide and its metabolites by liquid chromatography-tandem mass spectrometry
文献类型：期刊论文
| 作者 | Deng, Pan2; Chen, Xiaoyan2 ; Zhang, Guodong1; Zhong, Dafang2
|
| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
 |
| 出版日期 | 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. |
| WOS关键词 | INTERFERING RNA DUPLEX ; ANTISENSE OLIGONUCLEOTIDE ; PHOSPHOROTHIOATE OLIGONUCLEOTIDE ; THERAPEUTIC OLIGONUCLEOTIDES ; PLASMA ; QUANTIFICATION ; IDENTIFICATION ; RAFAON ; MOUSE ; ACIDS |
| 资助项目 | Pfizer Global Research and Development[00000000] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000276057300019 |
| 出版者 | ELSEVIER SCIENCE BV |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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