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Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice

文献类型：期刊论文

作者Yuan, Meng2,3; Hu, Wenjuan3; Feng, Yingying2,3; Tong, Yue1,3; Wang, Xin3; Tan, Bo4; Xu, Hui2; Liu, Jia3,5
刊名BIOMEDICAL CHROMATOGRAPHY
出版日期2022-04-13
页码10
关键词diabetic nephropathy LC-MS MS nucleoside pharmacokinetics remdesivir
ISSN号0269-3879
DOI10.1002/bmc.5380
通讯作者Xu, Hui(xuhui@ytu.edu.cn) ; Liu, Jia(jia.liu@simm.ac.cn)
英文摘要Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. Remdesivir is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, the phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5 '-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an Acquity HSS T-3 column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1,000 ng/ml for RDV and 5-10,000 ng/ml for both RM-442 and RN. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442 and RSD < 7.2% for RN) and accuracy (91.0-106.3% for RDV, 92.5-98.6% for RM-442 and 87.5-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in the blood of normal and diabetic nephropathy DBA/2 J mice after intravenous injection of RDV at 20 mg/kg. The area under the concentration-time curve of RN between the normal and diabetic nephropathy mice showed a significant difference (P < 0.01).
WOS关键词GS-5734 ; STABILITY ; EBOLA ; MODEL
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000782065000001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/299851]  
专题中国科学院上海药物研究所
通讯作者Xu, Hui; Liu, Jia
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Yantai Univ, Sch Pharm, Key Lab Mol Pharmacol & Drug Evaluat, Yantai 264005, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Clin Pharmacokinet Lab, Shuguang Hosp, Shanghai, Peoples R China
5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Yuan, Meng,Hu, Wenjuan,Feng, Yingying,et al. Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice[J]. BIOMEDICAL CHROMATOGRAPHY,2022:10.
APA Yuan, Meng.,Hu, Wenjuan.,Feng, Yingying.,Tong, Yue.,Wang, Xin.,...&Liu, Jia.(2022).Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice.BIOMEDICAL CHROMATOGRAPHY,10.
MLA Yuan, Meng,et al."Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice".BIOMEDICAL CHROMATOGRAPHY (2022):10.

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来源：上海药物研究所

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