Abstract

Background: Schiff base is an advanced key starting material of Sertraline hydrochloride. Schiff base is synthesized using two raw materials 1-Naphthol and 1,2-Dichlorobenzene which are potentially genotoxic impurities.

Objective: Genotoxic impurities need to be controlled in key starting material to avoid carry forward in the active pharmaceutical ingredient. For trace level quantification of impurities a sensitive, accurate and cost effective method is developed by simultaneous estimation of both impurities.

Methods: Reverse phase high performance liquid chromatography (HPLC) method was developed and validated for determination of both impurities in Schiff base. HPLC column Cosmosil MS-II C18, 100 mm X 4.6 mm, 3 μm particle size with ultra-violet detector (UV) was used.

Results: The calibration curve of 1-Naphthol and 1,2-Dichlorobenzene showed good linearity over the concentration range of 0.25 µg/g to 7.5 µg/g and 1.5 µg/g to 7.5 µg/g and the regression coefficient was 0.999 and 0.998 respectively. Method had very low limit of detection (LOD) and limit of quantification (LOQ) of both analytes which proves that the method is sensitive and suitable for quantification of compounds at trace level.

Conclusion: The proposed method is specific, linear, accurate, rugged and precise. Genotoxic impurities 1-Naphthol and 1,2-Dichlorobenzene are quantified and controlled in the key starting material of Sertraline hydrochloride. The validated method can be used in quality control unit in pharmaceutical industry.

Keywords: Sertraline, genotoxic, impurity, method development, validation, liquid chromatography.

Graphical Abstract