LC-MS/MS methods for direct measurement of sepiapterin and tetrahydrobiopterin in human plasma and clinical applications
Aim: Tetrahydrobiopterin (BH4), a natural cofactor of aromatic amino acid hydroxylases, and sepiapterin, a natural precursor of BH4, are endogenously present in human plasma. This is the first report on methods for direct quantification of sepiapterin and BH4 in human plasma by LC-MS/MS for pharmacokinetic assessment. Materials & methods: The analytes in plasma were harvested from blood that were treated with 10% ascorbic acid (AA) to a final concentration of 1% AA. Results & conclusion: The quantification methods were validated for calibration ranges of 0.75-500 ng/ml and 0.5-500 ng/ml for sepiapterin and BH4, respectively. Quantification of analytes was challenging due to their susceptibility to redox reactions. The validated methods were utilized successfully to support clinical development of sepiapterin.
| 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: 14. Jan., Seite 75-89 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kaushik, Diksha [VerfasserIn] |
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| Links: |
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| Themen: |
CJQ26KO7HP |
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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-2023-0144 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365902489 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Tetrahydrobiopterin (BH4), a natural cofactor of aromatic amino acid hydroxylases, and sepiapterin, a natural precursor of BH4, are endogenously present in human plasma. This is the first report on methods for direct quantification of sepiapterin and BH4 in human plasma by LC-MS/MS for pharmacokinetic assessment. Materials & methods: The analytes in plasma were harvested from blood that were treated with 10% ascorbic acid (AA) to a final concentration of 1% AA. Results & conclusion: The quantification methods were validated for calibration ranges of 0.75-500 ng/ml and 0.5-500 ng/ml for sepiapterin and BH4, respectively. Quantification of analytes was challenging due to their susceptibility to redox reactions. The validated methods were utilized successfully to support clinical development of sepiapterin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a LC–MS/MS | |
| 650 | 4 | |a endogenous | |
| 650 | 4 | |a method development | |
| 650 | 4 | |a pteridines | |
| 650 | 4 | |a quantification | |
| 650 | 4 | |a sample preparation | |
| 650 | 4 | |a sepiapterin | |
| 650 | 4 | |a stabilize | |
| 650 | 4 | |a tetrahydrobiopterin | |
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| 700 | 1 | |a Yuan, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Bowen |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Ronald |e verfasserin |4 aut | |
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