Development of Validated RP-HPLC Method for Determination of Sibutramine Applying QbD Approach

Sibutramine, {1-[1-(4-chlorophenyl) cyclobutyl]-3-methylbutyl} dethylamine is potent serotonin and norepinephrine inhibitor. Pharmacologically it acts as antihypertensive and anti- obesity agent via its secondary (M1) and primary (M2) amine metabolites. In present work an attempt has been done to develop a simple, rapid, precise and accurate isocratic reversed-phase HPLC method for the determination of sibutramine. As a novelty along with validation of developed method as per ICH guidelines, a QbD approach has been applied. As critical quality attributes related to analytical method have been identified and optimized more robustness and accurate method HPLC method has been developed. Slection of column, composition of mobile phase and flow rate were identified as critical quality attributes where by selection of KYA TECH HIQ Sil C18 (4.6 mm × 250 mm) 5μm column, Acetonitrile: water in composition 80:20 v/v as mobile phase with flow rate 1mL/min was done. The λmax was detected as 239 nm. The linearity range of the proposed method was found to be in the range of 10–50 μg/ml (r = 0.999). The limits of detection was 0.081 μg/ml and the limits of quantitation were 0.172 μg/ml respectively