A sensitive LC-MS/MS assay to quantitate free payload Aur0101 from ADC PYX-201 in rat and monkey plasma
Aim: Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody-drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Materials & methods: Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d8 were used in this LC-MS/MS method. Results: This sensitive assay was validated at a lower limit of quantitation of 15 pg/ml and successfully applied to support preclinical rat and monkey toxicology studies. Preclinical plasma toxicokinetic parameters were presented. Conclusion: A sensitive and robust LC-MS/MS assay was validated for Aur0101 in rat and monkey plasma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Bioanalysis - 15(2023), 14 vom: 16. Juli, Seite 833-843 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yin, Feng [VerfasserIn] |
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| Links: |
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| Themen: |
ADC |
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| Anmerkungen: |
Date Completed 07.09.2023 Date Revised 07.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/bio-2023-0056 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360836437 |
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| 245 | 1 | 2 | |a A sensitive LC-MS/MS assay to quantitate free payload Aur0101 from ADC PYX-201 in rat and monkey plasma |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody-drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Materials & methods: Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d8 were used in this LC-MS/MS method. Results: This sensitive assay was validated at a lower limit of quantitation of 15 pg/ml and successfully applied to support preclinical rat and monkey toxicology studies. Preclinical plasma toxicokinetic parameters were presented. Conclusion: A sensitive and robust LC-MS/MS assay was validated for Aur0101 in rat and monkey plasma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADC | |
| 650 | 4 | |a Aur0101 | |
| 650 | 4 | |a LC–MS/MS | |
| 650 | 4 | |a microtubule inhibitor | |
| 650 | 4 | |a oncology | |
| 650 | 4 | |a preclinical | |
| 650 | 4 | |a small molecule | |
| 650 | 4 | |a toxicokinetic | |
| 650 | 4 | |a validation | |
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| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 700 | 1 | |a Ahsan, Farah |e verfasserin |4 aut | |
| 700 | 1 | |a Pinkas, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Biplab |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Frank |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Nancy |e verfasserin |4 aut | |
| 700 | 1 | |a Hahn, David |e verfasserin |4 aut | |
| 700 | 1 | |a Amrite, Aniruddha |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jianwen |e verfasserin |4 aut | |
| 700 | 1 | |a Adhikari, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Sikora, Jack |e verfasserin |4 aut | |
| 700 | 1 | |a Shaheen, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Harriman, Shawn |e verfasserin |4 aut | |
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