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

doi:10.1002/jssc.202100491

	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
	Zhou, Jun 1; Zhan, Yan 2; Zhong, Dafang 2; Chen, Xiaoyan 2; Zhang, Yifan 2; Zhang, Qi 1; Bo, Yunhai 3; Shen, Lin 1; Gong, Jifang 1; Li, Jian 1
刊名	JOURNAL OF SEPARATION SCIENCE
	2021-09-09
页码	8
关键词	chimmitecan mass spectrometry pharmacokinetics simmitecan solid tumors
ISSN号	1615-9306
DOI	10.1002/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.
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关键词	ANTICANCER PRODRUG SIMMITECAN ; TOPOISOMERASE-I ; CAMPTOTHECIN ; DNA
WOS研究方向	Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000694635600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297854]
专题	中国科学院上海药物研究所
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.