Determination of chlorpromazine in the blood and brain of mice by high performance liquid chromatography combined with electrochemical detection.

A simple and sensitive procedure was developed for determining the concentration of chlorpromazine (CPZ) in the blood and brain of mice with promethazine as the internal standard. The procedure involves (1) primary extraction by a mixture of heptane and isoamyl alcohol (99:1) in an alkaline condition and (2) determination by means of high performance liquid chromatography with electrochemical detection. The detection limit of CPZ was 0.5 ng for one chromatographic injection. The drug was detectable in a 100 microliters sample of the blood by 6 hr after an intravenous injection of 0.25 mg/kg. The concentration of CPZ was about 40 times higher in the brain compared with that in the blood. The biological half life was estimated to be 87 and 65 min, in the blood and brain, respectively. The proposed method is also applicable for the determination of other phenothiazine derivatives and effective for pharmacokinetic study of the compounds in clinics and laboratories.