Automated gas chromatographic method for the determination of residual solvents in bulk pharmaceuticals

A generalized gas chromatographic method is described for the determination of a wide variety of residual solvents and other volatile impurities in bulk pharmaceuticals. The method employs a highly selective graphitized carbon-black stationary phase, which is demonstrated to retain compounds on the basis of a linear combination of their boiling points and molecular volumes (i.e., molecular weight divided by density). An autosampler is utilized to optimize injection precision and to provide for high sample throughput. Analytical data from replicate determinations of seven representative compounds are reported, and it is shown that calibration of the chromatographic systems against external standards produces comparable results to those obtained by standard addition techniques.