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
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.