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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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General Research Article

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

Author(s): Wenjun Zhou, Hongqun Qiao*, Lingling Xu, Yanjuan Yuan and Qing Shao

Volume 18, Issue 1, 2022

Published on: 11 December, 2020

Page: [101 - 110] Pages: 10

DOI: 10.2174/1573412917999201211204108

Price: $65

Abstract

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 C18 (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.

Keywords: R-α-lipoic acid, toxicokinetics, LC-MS/MS, isocratic elution, protein precipitation, sprague-dawley rats, intravenous injection.

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