生物分析および生物医学ジャーナル

Bioequivalence Study of Simvastatin

Abstract

Selvadurai Muralidharan, Janaki Sankarachari Krishnan Nagarajan, Sachin Singh and Anil Dubala

A simple, rapid and selective method was developed for esti- mation of simvastatin from human plasma. The method involves simple protein precipitation techniques using etofy lline as inter- nal standard. Chromatographic separation was carrie d out on a reversed phase C 18 column using mixture of methanol: 2mM ammonium acetate and 500 μl of 0.5% formic acid (80 :20, v/v) at a flow rate of 1.0 ml/min with UV-VIS detection at 418.35 nm. The retention time of simvastatin and internal standard were 5.41 and 1.086 min, respectively. The method was va lidated and found to be linear in the range of 1.0-10.0 ng/mL. An open, ran- domized, two-treatment, two period, single dose cro ssover, bioequivalence study in 12 fasting, healthy, male, volunteers was conducted. After dosing, serial blood samples were collected for the period of 24 . 0 h . Various pharmacokinetic parameters including AUC 0– t , AUC 0– ∞ , C max , T max , T ½ , and elimination rate constant ( K el ) were determined from plasma concentration of both formulations. Log transformed values were comp ared by nalysis of variance (ANOVA) followed by classical 90% con- fidence interval for C , AUC 0– t and AUC 0– ∞ and was found to be within the range. These results indicated that t he analytical method was linear, precise nd accurate. Test and r eference for- mulation were found to be bioequivalent.