Abstract

SIMPLE AND VALIDATED GAS CHROMATOGRAPHY METHOD FOR THE PURITY AND SINGLE MAXIMUM IMPURITY DETERMINATION OF 4-CHLORO BUTYRYL CHLORIDE; KSM OF LEVETIRACETAM API

Ramanjaneyulu Siddabathuni*, Venkatadri Tekuri, KMV Narayana Rao and Shyamala Pulipaka

ABSTRACT

A simple gas chromatographic (GC) method was developed for the determination of purity and single maximum impurity content for 4-Chloro butyryl chloride (4-CBC); 4-CBC is a key starting material for Levetiracetam drug substance. The purity method was optimized and validated using GC column DB-5 (30m×0.32mm, 0.25μm), 1.0 μL injection volume with a flow rate of 5.0 psi having injector temperature 250ºC and detector temperature 260ºC. The developed method could be accurately measure as low as 0.01% (LOQ) of 4-CBC and has a sensitivity of 0.003% (LOD). The new developed method displayed good linear range from LOQ (9.973 mg/mL) to 150 % level (149.595 mg/mL). The developed method was validated as per ICH Q2(R1) and USP validation of compendial methods (1225) and found to be the method is precise, accurate, linear and robust. Further, the method was displayed promising results for determination of purity, single maximum impurity in 4-CBC during the routine analysis. This new method has more advantages compared to the existing literature reported method (i.e., titration methods) in terms of sensitivity, selectivity, linear range, and most important future are could able to detect the single maximum unknown impurity also with purity.

Keywords: 4-Chloro butyryl chloride, Levetiracetam, GC, UV detector, Validation.