A simple, rapid, and reliable method to detect residual levels of tert-butanol in liposomes using sec-butanol as an internal standard has been developed. Solid-phase microextraction (SPME) followed by gas chromatographic analysis was used to quantify the amount of residual tert-butanol in freeze-dried liposome material. Only 1 min was necessary for reproducible amounts of analyte to absorb onto the SPME fiber, and because this method requires very little sample preparation, a single analysis can be completed in less than 15 min. This method had a linear range of 10-600 microg/mL. Careful control of times of temperature equilibration and exposure to headspace was necessary to ensure reproducible results. This method can easily be applied to other applications in the food and pharmaceutical industries where detection of residual solvents, such as hexane and chloroform, is necessary.