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dc.contributor.authorYin, Lei
dc.contributor.authorRen, Tianming
dc.contributor.authorZhao, Shiying
dc.contributor.authorShi, Meiyun
dc.contributor.authorGu, Jingkai
dc.date.accessioned2019-11-15T16:56:22Z
dc.date.available2019-11-15T16:56:22Z
dc.date.issued2020-01-01
dc.identifier.citationYin, L., Ren, T., Zhao, S., Shi, M., & Gu, J. (2020). Comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique. Talanta, 206, 120184.en_US
dc.identifier.issn0039-9140
dc.identifier.pmid31514844
dc.identifier.doi10.1016/j.talanta.2019.120184
dc.identifier.urihttp://hdl.handle.net/10150/635987
dc.description.abstractGemcitabine is a small molecular antitumor compound used to treat many types of solid tumors. The clinical application of gemcitabine is limited by its short biological half-life, rapid metabolism and poor tumor tissue targeting. The covalent attachment of polyethylene glycol to gemcitabine is a promising technique to overcome these limitations. After PEGylation, PEGylated gemcitabine could be metabolized into gemcitabine and its metabolites in vivo. Due to the scale effect of PEGylated gemcitabine, the DMPK process of the original drug is greatly changed. Therefore, understanding the pharmacokinetic behavior of PEGylated gemcitabine, gemcitabine and the metabolite dFdU in vivo is really important to clarify the antitumoral activity of these compounds. It would also guide the development of other PEGylated drugs. Due to the complex structure and diverse physiochemical property of PEG, direct quantification analysis of PEGylated gemcitabine presented many challenges in terms of assay sensitivity, selectivity, and robustness. In this article, a data-independent acquisition method, MSALL-based approach using electrospray ionization (ESI) coupled quadrupole time of flight mass spectrometry (MS), was utilized for the determination of PEGylated gemcitabine in rat plasma. The technique consists of a Q1 mass window through all the precursor ions, fragmenting and recording all product ions. PEGylated gemcitabine underwent dissociation in collision cell to generate a series of PEG related ions at m/z 89.0604, 133.0868, 177.1129 of 2, 3, 4 repeating ethylene oxide subunits and PEGylated gemcitabine related ions at m/z 112.0514. PEGylated gemcitabine was detected by the high resolution extracted ions based on the specific compound. For gemcitabine and dFdU, the study used derivatization of these high polarity compounds with dansyl chloride to improve their chromatographic retention. This paper describes comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique. The results show that PEGylation could reduce the drug clearance of the conjugated compounds and increase the drug plasma half-life. After administration of PEGylated gemcitabine, the exposure of the free gemcitabine in vivo is lower than administration of gemcitabine, which means that PEGylated gemcitabine possesses lower toxicity compared with gemcitabine.en_US
dc.description.sponsorshipNational Natural Science Foundation of ChinaNational Natural Science Foundation of China [81703607, 81430087, 81603182, 81673396, 81872831, 81773692]; Jilin Province Science and Technoligy Development plan project [20190103082JH]; Science and Technology Major Specialized Projects for "significant new drugs creation" of the 12th five-year plan [2012ZX09303-015, 2014ZX09303303]; National Key Technology R&D Program of the Ministry of Science and TechnologyNational Key Technology R&D Program [2012BA130B00]; CERS-China Equipment and Education Resources System [CERS-1-70]en_US
dc.language.isoenen_US
dc.publisherELSEVIERen_US
dc.rights© 2019 Elsevier B.V. All rights reserved.en_US
dc.subjectGemcitabineen_US
dc.subjectLC-MS/MSen_US
dc.subjectMS(ALL)en_US
dc.subjectPEGylated gemcitabineen_US
dc.subjectPharmacokineticen_US
dc.titleComparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MS techniqueen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Pharmen_US
dc.identifier.journalTALANTAen_US
dc.description.note24 month embargo; published online: 27 July 2019en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleTalanta


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