Abstract

Simple, trace level derivatization and liquid-liquid extraction method of a genotoxic impurity 2,4-dichlorobutanoic acid in antiepileptic drug substance: Levetiracetam by GC-MS technique.

Author(s): Saradhi Venkata Ramana V, Durga Raja K, Raghu Babu K, Padma M, Jagadeesh Kumar V, Pavan Kumar KSR, Hemant Kumar Sharma

The objective of this work was to develop and validate a simple derivatization and liquid–liquid extraction (LLE) procedure for GC-MS analysis of 2,4-Dichlorobutanoic acidor 2,4-Dichlorobutyric acidin Levetiracetam drug substance. The analyte was treated with methanol sulfuric acid mixture and extracted by water and n-Hexane, the supernatant allowed to separate into two phases, the derivative of analyte separated into the upper layer and detected by gas chromatography-mass spectrometry by using a short mid-polar capillary GC column at a high column-head pressure. Total run time of the analysis was15 min. Chromatographic conditions were achieved on DB-624 (6% cyanopropylphenyl and 94% dimethylpolysiloxane copolymer) capillary column (30 m long, 0.32 mm internal diameter, 1.8 μm diameter) using helium as a carrier gas at a flow rate of 1.5 mL/min.The process was optimized by a design of experiments.
Method validation parameters achieved as per regulatory requirements. The method was validated showing that the detection limit and quantitation limit of this impurity were 0.05 μg/g and 0.14 μg/g respectively. A good linearity over the 0.14-0.72 μg/g concentration range with correlation coefficient Ë? 0.999, providing satisfactory results in terms of intra-day and inter-day precision as well as an optimal accuracy.
Thus, proving that thedescribed GC-MS method could be employed for fast and simple analysis ofgenotoxic impurity 2,4-Dichlorobutanoic acid in Levetiracetam drug substance.

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