科研之友
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摘要
Bioequivalence studies of pharmaceutical preparations of medicinal endogenous substances are generally, lacking, as the endogenous background is the main obstacle for both experimental design and drug analysis. We conducted a single-dose, self-control, 3-period crossover study to evaluate the bioequivalence of a sustained-release versus an immediate-release preparation of potassium citrate for the treatment of urinany tract stones. This study included a placebo period to monitor the dynamics of endogenous plasma citrate, which could therefore be subtracted during the data processing. Notably, a new convenient method for plasma citrate determination utilizing ultrafiltration extraction and direct reversed-phase high-performance liquid chromatography (HPLC) was successfully applied in the study after validation. To our knowledge, this is first report using simple reversed-phase HPLC to analyze plasma citrate, and ultrafiltration also significantly simplified the plasma extraction procedure. HPLC was performed using all ODS column, with acetonitrile and 0.02 mol/l sulfuric acid (3:97 v/v) as the mobile phase and ultraviolet detection at 210 nm. Results showed linearity from 10 to 200 mu g/ml, an extraction recovery of more than 90% and analysis variability within 15% for additive citrate. The concentration of dog endogenous plasma citrate was determined to be about 30-40 mu g/ml. The sustained-release preparation was bioequivalent to the immediate-release preparation in terms of the extent of absorption, but it could not achieve full effects due to a t(max) issue.
- 出版日期2008-9
- 单位中国药科大学
