Identification, isolation, characterization and response factor determination of process-related impurity in meprobamate drug substance.

This paper describes identification and characterization of a process-related impurity of meprobamate drug substance observed in HPLC-UV method. Forced degradation studies were carried out under acidic, basic, oxidation, light and thermal conditions to assess the nature of the impurity. The pure impurity was obtained by preparative LC isolation and analyzed by NMR and mass. Structural elucidation by spectral data and formation of this impurity were discussed in detail. The structure of the process-related impurity was established as carbamic acid-2-carbamoyloxymethyl-2-methyl-pent-3-enyl ester (olefin). Also, the relative response factor, linearity, detection limit (DL), quantitation limit (QL) and recovery were determined for meprobamate and the impurity. Good linearity was obtained for the impurity over the concentration range of 0.03-0.20% (w/w) with the coefficient of determination (r(2)) of 0.999. The DL and QL of olefin impurity were 0.0003 and 0.001% (w/w), respectively. The isolated impurity was co-injected with meprobamate sample to confirm the retention time in HPLC.