A Quantitative LC-MS/MS Method for the Simultaneous Determination of the Presence of R-α-lipoic Acid and S-α-lipoic Acid After Protein Precipitation in Rat Plasma and its Application in a Toxicokinetic Study / Wenjun Zhou, Hongqun Qiao, Lingling Xu, Yanjuan Yuan, Qing Shao
Background: Lipoic acid is the only known chiral antioxidant that is both lipidsoluble and water-soluble. It is often used as a treatment for peripheral polyneuropathy caused by diabetes, alcohol, and chemicals. However, only a few long-term toxicological studies have been conducted on R-α-lipoic acid, which is a bioactive ingredient in lipoic acid. Objective: In this study, a simple, efficient, sensitive and stable LC-MS/MS method was used to determine RLA in rats, using deu-lipoic acid as an internal standard. Methods: The samples to be detected were plasma samples treated with protein precipitation and the simultaneous determination of the presence of R-α-lipoic acid and S-α-lipoic acid was conducted using LC-MS/MS. An isocratic elution program with a mobile phase composed of acetonitrile and 0.1% formic acid water solution (52/48) used for chromatographic separation was set up using a CHIRALPAK® IE C 18 (250 mm × 4.6 mm, 5 μm) column with a flow rate of 0.9 mL/min. A negative electrospray ionization source was chosen, and the multiple monitoring (MRM) mode was applied. Results: R-α-lipoic acid and S-α-lipoic acid both were found to be present at a linear range of 5- 5000 ng/mL. The plasma samples were stable under various storage conditions and temperatures. The toxicokinetics study indicated that there were gender differences and that R-α-lipoic acid showed bioaccumulative toxicity after long-term daily administration. In addition, R-α-lipoic acid and S-α-lipoic acid were not converted into each other in the rats. Conclusion: The method established was successfully used for the long-term toxicokinetic study of R-α-lipoic acid administered to rats through caudal vein injection. The toxicokinetics results indicated the presence of gender differences and the toxic accumulation of R-α-lipoic acid. The two enantiomers were not converted into each other in the rats.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Current pharmaceutical analysis - 18(2022), 1, Seite 10 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Wenjun [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (10 p) |
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| Förderinstitution / Projekttitel: |
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KFL011170026 |
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| 100 | 1 | |a Zhou, Wenjun |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Quantitative LC-MS/MS Method for the Simultaneous Determination of the Presence of R-α-lipoic Acid and S-α-lipoic Acid After Protein Precipitation in Rat Plasma and its Application in a Toxicokinetic Study |c Wenjun Zhou, Hongqun Qiao, Lingling Xu, Yanjuan Yuan, Qing Shao |
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| 520 | |a Background: Lipoic acid is the only known chiral antioxidant that is both lipidsoluble and water-soluble. It is often used as a treatment for peripheral polyneuropathy caused by diabetes, alcohol, and chemicals. However, only a few long-term toxicological studies have been conducted on R-α-lipoic acid, which is a bioactive ingredient in lipoic acid. Objective: In this study, a simple, efficient, sensitive and stable LC-MS/MS method was used to determine RLA in rats, using deu-lipoic acid as an internal standard. Methods: The samples to be detected were plasma samples treated with protein precipitation and the simultaneous determination of the presence of R-α-lipoic acid and S-α-lipoic acid was conducted using LC-MS/MS. An isocratic elution program with a mobile phase composed of acetonitrile and 0.1% formic acid water solution (52/48) used for chromatographic separation was set up using a CHIRALPAK® IE C 18 (250 mm × 4.6 mm, 5 μm) column with a flow rate of 0.9 mL/min. A negative electrospray ionization source was chosen, and the multiple monitoring (MRM) mode was applied. Results: R-α-lipoic acid and S-α-lipoic acid both were found to be present at a linear range of 5- 5000 ng/mL. The plasma samples were stable under various storage conditions and temperatures. The toxicokinetics study indicated that there were gender differences and that R-α-lipoic acid showed bioaccumulative toxicity after long-term daily administration. In addition, R-α-lipoic acid and S-α-lipoic acid were not converted into each other in the rats. Conclusion: The method established was successfully used for the long-term toxicokinetic study of R-α-lipoic acid administered to rats through caudal vein injection. The toxicokinetics results indicated the presence of gender differences and the toxic accumulation of R-α-lipoic acid. The two enantiomers were not converted into each other in the rats | ||
| 700 | 1 | |a Qiao, Hongqun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lingling |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Yanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Shao, Qing |e verfasserin |4 aut | |
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