AbstractA gas chromatographic chemical ionization mass spectrometric assay has been developed to measure carprofen in blood. The method features the addition of either a structural or stable isotope analog internal standard to plasma prior to a simple benzene extraction at pH 4.5. The residue, after removal of the benzene, is methylated with ethereal diazomethane. Following evaporation of the methylating solvents, a portion of the reconstituted residue is analyzed by gas chromatography mass spectrometry. The mass spectrometer is set to monitor in the gas chromatographic effluent the [MH]+ions of carprofen methyl ester and the methyl ester of internal standard generated by isobutane chemical ionization. Assay sensitivity is 5 pmol ml−1. When 200 pmol ml−1samples are analyzed using a stable isotope analog as the internal standard, the precision and accuracy are both 4%. Using a structural analog as the internal standard, the assay was neither as precise nor as accur