Quality-By-Design Based HPLC Method Development and Validation for Separation of Levosulpiride from Dosage Forms and Pharmacokinetic in Humans

Abstract

A novel quality by design-based high performance liquid chromatographic method was developed for levosulpiride. There was no specific method for levosulpiride in United States Pharmacopeia.
So, for the first time Quality by Design approach was implemented by Box- Behnken Design. Method specifications include; buffer (low molarity): acetonitrile (50:50), column c18, pH 7 and flow rate 0.6 mL/min.
Use of low molarity buffer increases the column life, 3.8 min fast retention time as compared with previously reported methods. A highly statistical significant model was obtained by employing Box- Behnken
Design with p value < 0.05. Chromatographic conditions selected within the Method Operable Design Region (MODR). Limit of detection in buffer/acetonitrile was 0.036 μg/mL, and the limit of quantification
was 0.11 μg/mL, however, limit of quantification in plasma was 18.57 ng/mL. The method was employed
successfully for assessment of levosulpiride in various pharmaceutical formulations. Additionally, the developed method was used for pharmacokinetic studies of four different dosage forms of levosulpiride in
human volunteers. The developed method is rapid, robust and sensitive and successfully employed for detection of levosulpiride in human plasma.