g-Hydroxybutyrate (GHB) and g-butyrolactone (GBL) are used as "date rape drugs" since they cause catalepsy and memory loss. A new application of secondary electrospray ionization (SESI) mass spectrometry for in situ detection of GHB and GBL in drinks and body fluids is introduced. Different mass spectrometers were compared, including a portable, miniaturized ion trap, a semi mobile benchtop ion trap, and a quadrupole time-of-flight instrument. Direct ionization of GHB and GBL from the headspace of drinks was shown, and the suitability for on-site measurements was tested. Several matrices including various drinks as well as body fluids such as urine and saliva were analyzed. SESI provides a robust, reliable, fast, and efficient ionization method, which is largely independent of the mass spectrometer and the matrix used. The detection limits for GHB and GBL in drinks were found to be always below 0.5 g L À1 , which is sufficient to identify them in beverages (a dose of about 2 g L À1 is commonly used). 8 mg L À1 GHB were detectable in urine, which suffices to identify an intoxicated individual. Overall, GHB and GBL can be detected in drinks and small leftovers of drinks as well as in body fluids at concentration levels that are of practical relevance. With a mobile MS instrument, this method could be applied as a diagnostic as well as a preventive on-site method.