A Novel QbD Based SPE-HPLC Bio-analytical Method for Edaravone in Rat Plasma, A Pharmacokinetic Study

摘要

A simple, sensitive and feasible Quality by design based RP-HPLC bioanalytical method was developed and validated for Edaravone. Plackett burman design and 3 square 3 full factorial designs were utilized for factor screening and optimization respectively, to achieve well resolved asymmetric peaks of both internal standard and drug with good theoretical plates. The optimized chromatographic peak was obtained with mobile phase composition of 10 mM ammonium acetate buffer (pH 6) and acetonitrile (60: 40, v/v) at a flow rate of 1.0 ml/m and detection wavelength of 243 nm using Kromasil C-18 (250 mm x 4.6 mm; 5 mu m) column. Non normality, skewness or outliers did not exist as demonstrated by residual plot. To eliminate the possible interferences in the biological matrices, a new solid-phase extraction method using STRATA X C-18 Phenomenex cartridges was developed and evaluated. The method was validated as per USFDA guideline. The developed method was efficiently applied to pharmacokinetic study in rat plasma.