Tapentadol enantiomers: Synthesis, physico-chemical characterization and cyclodextrin interactions
文献类型：期刊论文
| 作者 | Fejos, Ida1; He, Yang3; Volgyi, Gergely1; Kazsoki, Adrienn1; Sun, Jin3; Chen, Weiming3; Sohajda, Tamas2; Szente, Lajos2; Jiang, Xiangrui3 ; Beni, Szabolcs1
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| 刊名 | JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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| 出版日期 | 2014-01-25 |
| 卷号 | 88页码:594-601 |
| 关键词 | Enantioselective synthesis Chiral separation Protonation constant Migration order Capillary electrophoresis |
| ISSN号 | 0731-7085 |
| DOI | 10.1016/j.jpba.2013.10.005 |
| 文献子类 | Article |
| 英文摘要 | The complete physico-chemical characterization of the single enantiomer analgesic drug R,R-tapentadol was quantitated in terms of protonation macro- and microconstants and octanol-water partition coefficient using pH-potentiometry, UV-pH and H-1 NMR-pH titrations. The protonation macroconstants were found to be log K-1 = 10.59 +/- 0.01 and log K-2 = 9.44 +/- 0.01, while the individual basicity of each protonation site was found to be log k(o) = 9.94 and log k(N)= 10.48 for the phenolate and tertiary amine functions, respectively. As a consequence, the zwitterionic form of tapentadol predominates in aqueous solutions. The potential optical impurity (S,S-tapentadol) was synthesized for the first time in a seven-step chiral synthetic procedure. The enantiomers of tapentadol were separated by cyclodextrin modified capillary zone electrophoresis. Over 15 cyclodextrins were investigated in terms of apparent complex stability and screened as chiral selectors, and the sulfated alpha-cyclodextrin was found to resolve the enantiomers with excellent resolution (R-s = 16.2 and 9.1) at pH 4.75 and pH 9.0, respectively. The system containing 12 mM selector in a 50 mM IRIS-acetate buffer was amenable to detect S,S-tapentadol potential optical impurity at 0.1% concentration level. (C) 2013 Elsevier B.V. All rights reserved. |
| WOS关键词 | CAPILLARY-ELECTROPHORESIS METHOD ; CHIRAL RECOGNITION ; SPECTROSCOPY ; SEPARATION |
| 资助项目 | OTKA[PD 109373] ; Janos Bolyai Research Scholarship[00000000] ; National Science and Technology Major Project[2012ZX09301001-001] ; Key Project of Science and Technology of Shanghai[10431902800] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000329532800078 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277222]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Beni, Szabolcs |
| 作者单位 | 1.Semmelweis Univ, Dept Pharmaceut Chem, H-1092 Budapest, Hungary; 2.CycloLabRes & Dev Lab Ltd, H-1097 Budapest, Hungary 3.CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Fejos, Ida,He, Yang,Volgyi, Gergely,et al. Tapentadol enantiomers: Synthesis, physico-chemical characterization and cyclodextrin interactions[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2014,88:594-601. |
| APA | Fejos, Ida.,He, Yang.,Volgyi, Gergely.,Kazsoki, Adrienn.,Sun, Jin.,...&Beni, Szabolcs.(2014).Tapentadol enantiomers: Synthesis, physico-chemical characterization and cyclodextrin interactions.JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,88,594-601. |
| MLA | Fejos, Ida,et al."Tapentadol enantiomers: Synthesis, physico-chemical characterization and cyclodextrin interactions".JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 88(2014):594-601. |
入库方式： OAI收割
来源：上海药物研究所
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