Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies
DC Field | Value | Language |
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dc.contributor.author | Thi-Thao-Linh Nguyen | - |
dc.contributor.author | Kim, Jin Woo | - |
dc.contributor.author | Choi, Hae-In | - |
dc.contributor.author | Maeng, Han-Joo | - |
dc.contributor.author | Koo, Tae-Sung | - |
dc.date.accessioned | 2022-04-19T08:40:26Z | - |
dc.date.available | 2022-04-19T08:40:26Z | - |
dc.date.created | 2022-04-19 | - |
dc.date.issued | 2022-03 | - |
dc.identifier.issn | 1420-3049 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84057 | - |
dc.description.abstract | ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clinical trials. However, there is a lack of bioanalytical assays for ARV-110 determination in biological samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water-0.1% formic acid in acetonitrile (30:70, v/v). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 -> 452.2 and 273.8 -> 201.0, respectively. The developed method showed good linearity in the concentration range of 2-3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37 degrees C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, respectively). These pharmacokinetic findings are beneficial for future preclinical and clinical studies of ARV-110 and/or other PROTACs. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.relation.isPartOf | MOLECULES | - |
dc.title | Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000776312900001 | - |
dc.identifier.doi | 10.3390/molecules27061977 | - |
dc.identifier.bibliographicCitation | MOLECULES, v.27, no.6 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85127172112 | - |
dc.citation.title | MOLECULES | - |
dc.citation.volume | 27 | - |
dc.citation.number | 6 | - |
dc.contributor.affiliatedAuthor | Thi-Thao-Linh Nguyen | - |
dc.contributor.affiliatedAuthor | Maeng, Han-Joo | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | ARV-110 | - |
dc.subject.keywordAuthor | proteolysis-targeting chimera | - |
dc.subject.keywordAuthor | LC-MS | - |
dc.subject.keywordAuthor | MS | - |
dc.subject.keywordAuthor | validation | - |
dc.subject.keywordAuthor | stability | - |
dc.subject.keywordAuthor | pharmacokinetics | - |
dc.subject.keywordPlus | CHROMATOGRAPHY-TANDEM MASS | - |
dc.subject.keywordPlus | MOUSE PLASMA | - |
dc.subject.keywordPlus | SPECTROMETRY | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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