Sulpiride (SU), a benzamide neuroleptic, its N-methyl and N-propyl homologs (ME-SU and PR-SU) and 6 of its metabolites (DEALK-SU, O-DESM-SU, O-DESM-DEALK-SU, OXO-SU, O-DESM-OXO-SU and DEPYR-SU) have been quantified at the low ng level with an off-line LC-MS technique. This technique involves high pressure liquid chromatography separation and direct probe chemical ionization mass spectrometry with the use of a homolog as internal standard for the entire procedure. Selected ion monitoring of the (M + H)⁺ ions of Sulpiride and the internal standard and the ratio of the integrated ion currents were used for quantification. This method was used for the determination of two structurally different tissues of the hypophysis of rats.