HPLC determination of anethole trithione and its application to pharmacokinetics in rabbits

To evaluate the relative bioavailability of anethole trithione (ATT) from self-microemulsifying drug delivery system (SMEDDS) and tablet, a sensitive, accurate and reliable liquid chromatography method was developed and validated to determine ATT in rabbit plasma. Chromatographic separation was performed on a Diamonsil C-18 column by using a mixture of methanol-water (90:10, v/v) delivered at a flow rate of 1.0 ml/min. The wavelength was set at 348 nm and mifepristone was used as the internal standard. A linear relationship for ATT was found in the range of 0.5-32 ng/ml. The mean extraction recoveries of ATT determined over three concentrations were 84.7 +/- 5.8, 92.3 +/- 3.4 and 89.9 +/- 5.1%. After administration of SMEDDS and tablets to rabbits, significant differences were found in main pharmacokinetic parameters of T-max, C-max and AUC(0-infinity) between these two formulations, and a 2.5-fold enhancement of relative bioavailability of ATT was observed from the SMEDDS compared with tablets. (c) 2006 Elsevier B.V. All rights reserved.