Abstract Fused-silica columns of 0.22 mm I.D. packed with normal small-particle high-performance liquid chromatography packing material were studied. The shape of the column end allows direct connection to a combined electron impact—chemical ionization (EI—CI) ion source. To inject small volumes a syringe-loaded micro-sample injector is used with the time splitting technique. Mass spectra obtained from easily vaporized compounds are similar to, but display less thermal decomposition than, normal EI spectra. Mass spectra of underivatized native mono- and disaccharides give useful structural information. Results from the analysis of cardiac glucosides are also shown. The system provides high-efficiency chromatography with a universal detector, suitable for the analysis of non-volatile and labile compounds.