Wenjun Zhou, Hongqun Qiao*, Lingling Xu, Yanjuan Yuan and Qing Shao Pages 1 - 11 ( 11 )
Abstract: Background: Lipoic acid is the only known chiral antioxidant that is both lipid-soluble 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.
Method: 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.
Conclusions: 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.
R-α-lipoic acid, Toxicokinetics, LC-MS/MS, Isocratic elution, Protein precipitation, Sprague-Dawley rats, Intravenous injection
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816,, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816,, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816,, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816,, Jiangsu Provincial Institute Of Materia Medica, Nanjing 211816