Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR.
机构：[1]State Key Laboratory of Bioactive Substance and Function ofNatural Medicines, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, No. 2 Nanwei Street, Xicheng District, Beijing 100050, China[2]Jiuzhang Biochemical Engineering Science and Technology Development Co., Ltd., Chengdu, Sichuan 610041, China[3]Department of Glioma, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
A novel anti-tumor candidate drug, 5-chlorogenic acid (5-CQA) injection, was used for the treatment of malignant glioma in clinical trial (phase I) in China. The isolation and identification of the metabolites of 5-CQA injection in humans were investigated in the present study. Urine and feces samples obtained after intramuscular administration of 5-CQA injection to healthy adults have been analyzed by high-performance liquid chromatography coupled with high-resolution mass and multiple-stage mass spectrometry (HPLC-HRMS/MSn). No metabolite was detected in human feces; however, in human urine, a total of six metabolites were identified including isomerized 5-CQA (P1 and P2), hydrolyzed 5-CQA (M1and M2), and methylated 5-CQA (M3 and M4). Among them, M3 and M4 were the main metabolites and target analytes for human mass balance study. Additionally, the structure of M3 and M4 was characterized by high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance (HPLC-SPE-NMR), and the results demonstrated that the methoxy group of M3 and M4 was exclusively attributed to C-3' and C-4', respectively. Due to the unavailability of commercial reference, the pure products of M3 and M4 were synthesized by 5-CQA methylation and followed by isolation and purification. Moreover, the potential activity of M3 and M4 on malignant glioma was predicted using a reverse molecular docking analysis on eight malignant glioma-related pathways. The results showed that M3 and M4 had various interactions against malignant glioma-related targets. Our study provides an insight into the metabolism of 5-CQA injection in humans and supports the clinical human mass balance study. Graphical abstract ᅟ.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|3 区化学
小类|2 区分析化学3 区生化研究方法
最新[2023]版：
大类|2 区化学
小类|3 区生化研究方法3 区分析化学
第一作者：
第一作者机构：[1]State Key Laboratory of Bioactive Substance and Function ofNatural Medicines, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, No. 2 Nanwei Street, Xicheng District, Beijing 100050, China
通讯作者：
通讯机构：[1]State Key Laboratory of Bioactive Substance and Function ofNatural Medicines, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, No. 2 Nanwei Street, Xicheng District, Beijing 100050, China[3]Department of Glioma, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
推荐引用方式(GB/T 7714)：
Tiankun Ren,Yanan Wang,Caihong Wang,et al.Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR.[J].Analytical and bioanalytical chemistry.2017,409(30):7035-7048.doi:10.1007/s00216-017-0657-3.
APA：
Tiankun Ren,Yanan Wang,Caihong Wang,Mengtian Zhang,Wang Huang...&Jinlan Zhang.(2017).Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR..Analytical and bioanalytical chemistry,409,(30)
MLA：
Tiankun Ren,et al."Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR.".Analytical and bioanalytical chemistry 409..30(2017):7035-7048
