High-performance liquid chromatography with UV detection (HPLC-UV) and gas chromatography with either nitrogen phosphorus (GC-NPD) or mass spectrometry (GC-MS) detection were used for the determination of ticlopidine in plasma. Solid-phase extraction of ticlopidine from plasma was performed using Extrelut columns without pH adjustment, and using hexane as the solvent of elution. With HPLC, a mobile phase of 0.01 M pH 7.8 phosphate buffer:acetonitrile (70:30) was passed through a mu Bondapack C-18 column at a rate of 1.3 mL/min. Ultraviolet detection at 235 nm was sensitive to plasma ticlopidine concentrations of 0.05 micrograms/mL. The GC-NPD and GC-MS were performed on a DB-17 fused-silica column using on-column injection. For GC-NPD and GC-MS, limits of quantification were found to be 0.020 and 0.005 micrograms/mL, respectively. Compared with HPLC-UV, the GC methods were found to be more reproducible, sensitive, and specific and therefore more suitable for pharmacokinetic applications.