Metabolite identification and quantitation of RBD1016 siRNA : a direct comparison of hybridization-based LC-FD and LC-HRAM assays
Aim: RBD1016 is an N-acetylgalactosamine-conjugated siRNA drug currently in a phase II trial for treatment of chronic hepatitis B virus. To evaluate its absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic/pharmacodynamic (PK/PD) properties, two LC-based bioanalytical methods, LC-high-resolution/accuracy MS and LC-fluorescence detection, were developed and qualified. Materials & methods: The LC-high-resolution/accuracy MS method was used for metabolite identification and simultaneous quantitation of the antisense and sense strands as well as their respective metabolites. The LC-fluorescence detection assay was primarily used for analyzing the antisense strand and its metabolites in low-concentration plasma samples. The two methods were successfully bridged by analyzing the same sets of study samples. Results & conclusion: Both methods were found to have excellent accuracy/precision, specificity and reproducibility to support ADME and PK/PD studies of RBD1016 siRNA.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Bioanalysis - 16(2023), 2 vom: 01. Jan., Seite 91-105 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ji, Yuhuan [VerfasserIn] |
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| Links: |
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| Themen: |
Bioanalysis |
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| Anmerkungen: |
Date Completed 22.12.2023 Date Revised 22.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/bio-2023-0161 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364574704 |
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| 245 | 1 | 0 | |a Metabolite identification and quantitation of RBD1016 siRNA |b a direct comparison of hybridization-based LC-FD and LC-HRAM assays |
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| 500 | |a Date Revised 22.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: RBD1016 is an N-acetylgalactosamine-conjugated siRNA drug currently in a phase II trial for treatment of chronic hepatitis B virus. To evaluate its absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic/pharmacodynamic (PK/PD) properties, two LC-based bioanalytical methods, LC-high-resolution/accuracy MS and LC-fluorescence detection, were developed and qualified. Materials & methods: The LC-high-resolution/accuracy MS method was used for metabolite identification and simultaneous quantitation of the antisense and sense strands as well as their respective metabolites. The LC-fluorescence detection assay was primarily used for analyzing the antisense strand and its metabolites in low-concentration plasma samples. The two methods were successfully bridged by analyzing the same sets of study samples. Results & conclusion: Both methods were found to have excellent accuracy/precision, specificity and reproducibility to support ADME and PK/PD studies of RBD1016 siRNA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a LC–high-resolution/accuracy MS | |
| 650 | 4 | |a bioanalysis | |
| 650 | 4 | |a hybridization-based LC–fluorescence detection | |
| 650 | 4 | |a metabolite identification | |
| 650 | 4 | |a metabolite quantitation | |
| 650 | 4 | |a siRNA | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 700 | 1 | |a Guo, Zhaoxu |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Limin |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Yantao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Laixin |e verfasserin |4 aut | |
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