Investigation of on-line reversed-phase liquid chromatography–gas chromatography–mass spectrometry as a tool for the identification of impurities in drug substances

Abstract

The potential of on-line reversed-phase (RP) LC–GC–MS for the identification of impurities in pharmaceutical products has been investigated. The technical aspects of the system were studied using the potential drug eltoprazine as test compound. After LC separation on a 2 mm id RPLC column, using 5 mmol l–1 methanesulfonic acid in acetonitrile–water (84 + 16 v/v) as eluent, the eltoprazine-containing fraction of 200 µl was introduced on-line into the GC–MS, the mass spectrometer being a magnetic sector instrument. Before this introduction, the methanesulfonic acid was removed on-line from the LC eluent via an anion-exchange membrane. Most of the solvent introduced into the GC–MS was evaporated via a solvent vapour exit installed in front of the capillary GC column. As an application, impurity profiling was performed on the drug substance mebeverine which contained mebeverine amine as test impurity. The addition of acetonitrile was necessary before introduction into the GC; therefore only about 10% v/v of the mebeverine amine LC peak was transferred to the GC–MS. Nevertheless, electron impact and chemical ionization spectra of the impurity could be obtained at a level of 0.1% with respect to the drug.