The development of separation methods for residual solvents in pharmaceutical materials

This thesis describes the development of separation methods of known residual solvents from pharmaceutical materials, using static headspace and gas chromatograph flame ionization (GC FID). This detection was developed to improve upon the European Pharmacopeia methods for possible U.S. Pharmacopeia adoption. Appropriate static loop headspace and GC FID parameters were established to detect and quantify 62 possible residual solvents, for application with water-insoluble pharmaceutical materials, while static syringe headspace parameters were established for use with water-soluble materials. All parameters were established to detect residual solvents below their acceptable daily exposure limits. Quantitation of Class One residual solvents were variable, while Class Twos were not. This inconsistency was even larger when using the static headspace equipment. Variability was reduced when additional dimethyl sulfoxide was added to preparations.