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A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor

文献类型：期刊论文

作者Zhou, Jun1; Zhan, Yan2; Zhong, Dafang2; Chen, Xiaoyan2; Zhang, Yifan2; Zhang, Qi1; Bo, Yunhai3; Shen, Lin1; Gong, Jifang1; Li, Jian1
刊名JOURNAL OF SEPARATION SCIENCE
出版日期2021-09-09
页码8
关键词chimmitecan mass spectrometry pharmacokinetics simmitecan solid tumors
ISSN号1615-9306
DOI10.1002/jssc.202100491
通讯作者Li, Jian(oncogene@163.com) ; Yang, Fen(yf7854@163.com)
英文摘要Simmitecan is a new ester anticancer prodrug which can exert the antiproliferation activity through its active metabolite, chimmitecan. In the current study, a simple and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of simmitecan and chimmitecan in human plasma. Both irinotecan and 7-ethyl-10-hydroxycamptothecin were used as the internal standards. Plasma samples were protein precipitated by acetonitrile (0.2% formic acid, v/v) and processed samples were chromatographed on a Hypersil GOLD(TM) C-18 column (100 x 4.6 mm, i.d. 3.0 mu m) with acetonitrile and 10 mM ammonium acetate (0.1% formic acid, v/v) as the mobile phase. The calibration curves showed good linearity (R >= 0.99) over the concentration range of 1-500 ng/mL and 0.25-125 ng/mL for simmitecan and chimmitecan, respectively. Intra- and inter-run precisions (CV%) were <= 10.2% for simmitecan and <= 12.1% for chimmitecan. The accuracies were 99.4-103.5% for simmitecan and 95.4-103.5% for chimmitecan. This method was further successfully applied to a pharmacokinetic study of simmitecan in Chinese advanced solid cancer patients after administration of simmitecan hydrochloride injection.
WOS关键词ANTICANCER PRODRUG SIMMITECAN ; TOPOISOMERASE-I ; CAMPTOTHECIN ; DNA
资助项目NationalNatural Science Foundation of China[82073817] ; NationalNatural Science Foundation of China[81602655] ; Science Foundation of Peking University Cancer Hospital[2021-3]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000694635600001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/297854]  
专题新药研究国家重点实验室
通讯作者Li, Jian; Yang, Fen
作者单位1.Peking Univ, Dept Gastrointestinal Oncol, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Canc Hosp & Inst, Beijing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
3.Peking Univ, Natl Drug Clin Trial Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ,Canc Hosp & Inst, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Jun,Zhan, Yan,Zhong, Dafang,et al. A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor[J]. JOURNAL OF SEPARATION SCIENCE,2021:8.
APA Zhou, Jun.,Zhan, Yan.,Zhong, Dafang.,Chen, Xiaoyan.,Zhang, Yifan.,...&Yang, Fen.(2021).A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor.JOURNAL OF SEPARATION SCIENCE,8.
MLA Zhou, Jun,et al."A validated HPLC-MS/MS method for determination of simmitecan and its metabolite chimmitecan in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor".JOURNAL OF SEPARATION SCIENCE (2021):8.

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来源：上海药物研究所

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