Determination of the quinidine analog, 7'-trifluoromethyldihydrocinchonidine-2HCl in plasma and urine by high-performance liquid chromatography.

A rapid and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of the antiarrhythmic quinidine analog, 7'-trifluoromethyldihydrocinchonidine.2HCl ([I].2HCl) in plasma and urine. The overall recovery of [I] from plasma was 86 +/- 9% with a sensitivity limit of detection of 0.2 microgram/ml. The assay involves extraction of [I] into benzene--methylene chloride (9:1) from plasma or urine made alkaline with 0.1 N sodium hydroxide (pH 13) and saturated sodium chloride, the residue of which is dissolved in methylene chloride, an aliquot of which is analyzed by HPLC using adsorption chromatography on silica gel with UV detection at 254 nm. The mobile phase composed of methylene chloride--methanol--conc. ammonium hydroxide (95.5:4:0.5) yields baseline resolution of quinidine used as the internal (reference) standard, compound [I] and dihydroquinidine, a common contaminant in quinidine. The assay was applied to the analysis of plasma and urine samples taken from a dog administered a single 20 mg/kg dose via intravenous and oral routes. The stability of [I] in human plasma for up to 37 days of storage at -17 degrees C was also demonstrated.