A sensitive and specific method is presented for the quantification of disopyramide, a new antiarrhythmic agent, in blood plasma or serum. Aminopentamide, a chemically similar compound, is added to the biological fluid, and the two compounds are extracted with chloroform. The concentrated extract is treated with trifluoroacetic anhydride, resulting in the dehydration of the primary amide group of the drug and internal standard to the corresponding nitriles. The dehydrated derivatives are gas chromatographed and detected using a nitrogen-phosphorus detector. The method is applicable to the determination of the drug in plasma in the 1–10 µg/mL concentration range.