Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases
文献类型：期刊论文
| 作者 | Hu, Zheyi1; Sun, Yan1,2; Du, Feifei; Niu, Wei; Xu, Fang; Huang, Yuxing; Li, Chuan1
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| 刊名 | JOURNAL OF CHROMATOGRAPHY A
 |
| 出版日期 | 2011-09-23 |
| 卷号 | 1218期号:38页码:6646-6653 |
| 关键词 | Simmitecan Chimmitecan Irinotecan Camptothecin Prodrug Carboxylesterase Bis(4-nitrophenyl)phosphate Pulse gradient chromatography Matrix effects |
| ISSN号 | 0021-9673 |
| DOI | 10.1016/j.chroma.2011.07.042 |
| 文献子类 | Article |
| 英文摘要 | Simmitecan (L-P) is an anticancer ester prodrug, which involves activation to chimmitecan (L-2-Z). In the current study, a liquid chromatography/tandem mass spectrometry-based method was developed for simultaneous determination of L-P and L-2-Z in various plasma samples. Because L-P is rapidly converted to L-2-Z by blood carboxylesterase during and after sampling, which hampers accurate determination of L-P and L-2-Z in the biological samples, different carboxylesterase inhibitors were tested. As a result, bis(4-nitrophenyl)phosphate gave the best results with respect to inhibitory capability, hemolysis, and matrix effects and was used to deactivate blood carboxylesterases when sampling. The plasma samples were precipitated with acetonitrile and the resulting supernatants were separated using a pulse gradient method on a C18 column. Irinotecan and camptothecin were used as internal standards for quantification of L-P and L-2-Z, respectively. Protonated L-P, L-2-Z and their internal standards were generated by electrospray ionization and their precursor-product ion pairs (m/z 599 -> 124,405 -> 361,587 -> 195, and 349 -> 305, respectively) were used for measurement. The newly developed bioanalytical assay processed favorable accuracy and precision with lower limits of quantification of 2.1 nM for L-P and 3.4 nM for L-2-Z, and was successfully applied to pharmacokinetic studies in tumor-bearing nude mice, rats, and dogs. There are substantial species differences in the ester activity. The experimental strategies illustrated in our report may be adopted for measurement of other prodrugs (including irinotecan) or drugs subject to ester hydrolysis, as well as their metabolites, in biological matrices. (C) 2011 Elsevier B.V. All rights reserved. |
| WOS关键词 | LIQUID-CHROMATOGRAPHIC METHOD ; CAMPTOTHECIN DERIVATIVE IRINOTECAN ; HUMAN INTESTINAL CARBOXYLESTERASE ; CARBOXYLATE FORMS ; RAT PLASMA ; SIMULTANEOUS QUANTITATION ; LACTONE FORMS ; IN-VIVO ; PERFORMANCE ; CPT-11 |
| 资助项目 | National Science Fund of China for Distinguished Young Scholars[30925044] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09304-002] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09301-001] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09102-020] ; Shanghai Science and Technology Major Project[08DZ1980200] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000295432700009 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278398]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Sun, Yan |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Lab DMPK Res Herbal Med, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Hu, Zheyi,Sun, Yan,Du, Feifei,et al. Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases[J]. JOURNAL OF CHROMATOGRAPHY A,2011,1218(38):6646-6653. |
| APA | Hu, Zheyi.,Sun, Yan.,Du, Feifei.,Niu, Wei.,Xu, Fang.,...&Li, Chuan.(2011).Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases.JOURNAL OF CHROMATOGRAPHY A,1218(38),6646-6653. |
| MLA | Hu, Zheyi,et al."Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases".JOURNAL OF CHROMATOGRAPHY A 1218.38(2011):6646-6653. |
入库方式： OAI收割
来源：上海药物研究所
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