An analytical method for the determination of tranilast in human plasma using tramadol as the internal standard has been developed based on liquid chromatography/tandem mass spectrometry. Sample preparation involved protein precipitation with methanol. Separation by reversed-phase high-performance liquid chromatography using methanol/10 mM ammonium acetate (70: 30, v/v) as mobile phase was complete in a run time of 2.4 min. Detection on a Q TRAP™ system used multiple reaction monitoring. The method was linear in the range 0.06–20 µg/mL with intra- and inter-day precisions (as relative standard deviation) of 2.2–2.6% and 2.3–2.9%, respectively. Accuracy (as relative error) was <−2.5%. The method was applied in a pharmacokinetic study in healthy volunteers treated with a single 80 mg oral dose of tranilast. Copyright © 2006 John Wiley & Sons, Ltd.