Challenges and recommendations in developing LC-MS/MS bioanalytical assays of labile glucuronides and parent compounds in the presence of glucuronide metabolites
Glucuronides, especially acyl glucuronides, were often found to be unstable in vitro and in vivo. Acyl glucuronide metabolites can convert back to the parent drugs at physiological pH through hydrolysis. Glucuronides can also undergo in-source fragmentation during MS ionization to form the same ions as those of the parent compounds, which could cause interference to the analysis of the parent compounds. All of these may cause significant challenges in developing LC-MS/MS bioanalytical assays of labile glucuronides or parent compounds in the presence of glucuronide metabolites. In this manuscript, we will discuss these challenges and summarize recommended strategies and practices for fast and efficient method development. Critical considerations in assay development will also be discussed.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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Enthalten in: |
Bioanalysis - 12(2020), 9 vom: 10. Mai, Seite 615-624 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yuan, Long [VerfasserIn] |
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Links: |
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Themen: |
Acyl glucuronides |
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Anmerkungen: |
Date Completed 26.01.2021 Date Revised 26.01.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.4155/bio-2020-0055 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM310237734 |
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520 | |a Glucuronides, especially acyl glucuronides, were often found to be unstable in vitro and in vivo. Acyl glucuronide metabolites can convert back to the parent drugs at physiological pH through hydrolysis. Glucuronides can also undergo in-source fragmentation during MS ionization to form the same ions as those of the parent compounds, which could cause interference to the analysis of the parent compounds. All of these may cause significant challenges in developing LC-MS/MS bioanalytical assays of labile glucuronides or parent compounds in the presence of glucuronide metabolites. In this manuscript, we will discuss these challenges and summarize recommended strategies and practices for fast and efficient method development. Critical considerations in assay development will also be discussed | ||
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