Improved liquid-chromatographic assay of quinidine and its metabolites in biological fluids.

We describe a simple, rapid, and specific assay for quinidine and its known metabolites in plasma, urine, and bile. Plasma proteins are precipitated by adding acetonitrile, which also contains the internal standard. The supernatant fluid is evaporated and the reconstituted residue is separated on a reversed-phase column, with fluorescence detection. The standard curve is linear and results are reproducible over the clinical concentration ranges: quinidine 0.4 to 8.0 mg/L and the three metabolites (quinidine 10,11-diol, 3-hydroxyquinidine, and quinidine-N-oxide) 0.05 to 1.5 mg/L. As little as 10 micrograms of the N-oxide metabolite per liter and 1 microgram of the other analytes per liter can be quantitated in 0.5 mL of plasma, urine, or bile. With the use of an automated chromatographic system, many samples can be analyzed in a continuous run.