Analysis of the Genotoxic Impurity S-(+)-Epichlorohydrin Contained in (S)-Oxiracetam using Gas Chromatography

Background: (S)-oxiracetam has shown better efficacy than racemic oxiracetam in the trial. However, there is no report on the method used to detect the genotoxic impurity of S-(+)-epichlorohydrin(S-(+)-ECH) that may be contained in (S)-oxiracetam. Objective: Here, we have proposed and verified a detailed analysis method for the (S-(+)-ECH) impurity in (S)-oxiracetam using a gas chromatography(GC) system. Methods: The chromatography system includes a Supelco DB-624 capillary column. The initial column temperature was 50 degrees C, kept for 4 minutes, and then increased to 220 degrees C at a rate of 10 degrees C/min for 4 minutes. Nitrogen was used as the carrier gas. The constant flow rate was 3.8 mL/min, the split ratio was 10:1, the injection port temperature was maintained at 200 degrees C, and a hydrogen flame ionization detector was used. S-(+)-ECH was analyzed in detail by this analysis method, and three different batches of samples were measured. The GC system was used for verification. Results: The method verification results included the system suitability, specificity, sensitivity, accuracy, precision, and the good correlation coefficient between peak responses and concentrations were over 0.990. Conclusion: The method proposed in this study is the most detailed GC method currently used for the analysis of S-(+)-ECH impurities in (S)-oxiracetam. The proposed method has the advantages of fast, convenience, low cost, etc. It provides a reference method for quality control of genotoxic impurity of (S)-oxiracetam.

Automated summary

This study proposed and verified a detailed GC method for the analysis of S-(+)-ECH impurities in (S)-oxiracetam. The method has the advantages of fast, convenience, and low cost, providing a reference method for quality control.