Study on bioequivalence of beraprost in healthy volunteers by liquid chromatography with tandem mass spectrometry.

Beraprost sodium is an oral prostacyclin analog that was first approved in 1992 (Japan) for the treatment of peripheral vascular disorders. It is administered orally as a tablet available in strength 20 µg. In this paper, we described a liquid chromatography tandem mass spectrometry method that was developed for the quantification of beraprost in human plasma with high sensitivity at picogram per milliliter concentration. The method had been validated in terms of selectivity, sensitivity, accuracy and precision, matrix effect, linearity, recovery and carry-over according to the Guideline on Bioanalytical Validation from the European Medicines Agency. The standard calibration curve for beraprost was 9.5-1419 pg/mL. This method has been applied successfully to a bioequivalence study with 60 µg of beraprost (three tablets) in 29 healthy volunteers. The results showed that the two formulations of beraprost are bioequivalent.

Impact of Truncated Area on Point Estimate and Intra-Subject Variability in Bioequivalence of Dutasteride with Long Half-Life.

PURPOSE: To investigate the effect of using truncated area under the curve (AUC0-72) on bioequivalence of dutasteride with long half-life in point estimate and intra-subject variability. METHODS: Fifteen subjects were enrolled in this single-dose, open-label, randomized two-way crossover design following an overnight fasting with five-week washout period. Plasma samples were collected to 72 h and 144 h following drug administration and dutasteride were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The pharmacokinetic parameters for bioequivalence assessment were AUC0-72 and AUC0-144. RESULTS: The estimated point and the 90% confidence intervals were 91.07% (84.54-98.11%) for AUC0-72 and 91.43% (84.65-98.75%) for AUC0-144, that is, within the ranges for acceptance of bioequivalence. The intra-subject variability's were 11.45% for AUC0-72 and 11.87% for AUC0-144. CONCLUSIONS: There was no statistically significant difference in point estimated and intra-subject variability between truncated AUC at 72 h and 144=h and the truncated AUC (AUC0-72) approach could be considered for bioequivalence assessment for dutasteride.