SENSITIVE METHOD FOR THE SIMULTANEOUS MEASUREMENT OF FLUPHENAZINE DECANOATE AND FLUPHENAZINE IN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH COULOMETRIC DETECTION

A highly sensitive and specific high-performance liquid chromatographi c method with coulometric detection was developed for the simultaneous assay of fluphenazine decanoate and fluphenazine in plasma. The extra ction and sample clean-up procedures are simple, rapid to execute, yet yield chromatograms relatively free of any interference from endogeno us plasma constituents, such that the extraordinary sensitivity of the coulometric detector can be exploited fully. This is the first analyt ical procedure for the simultaneous determination of fluphenazine deca noate and fluphenazine. The detection limits for both fluphenazine dec anoate and fluphenazine were 0.1 ng/ml plasma and the limits of quanti tation were 0.25 ng/ml plasma. Standard curves from 0.25 to 10 ng/ml w ere linear with coefficients of variation <10%. The method was applied to measure plasma levels of fluphenazine decanoate and fluphenazine i n patients under medication with 25-50 mg biweekly intramuscular (i.m. ) injections of fluphenazine decanoate. It was possible to monitor the plasma levels of fluphenazine in all cases. Fluphenazine decanoate wa s present in measurable concentration in the plasma of 4 out of 5 pati ents who received biweekly i.m. injections of 50 mg fluphenazine decan oate. In a pilot experiment with a dog, the method was used to follow fluphenazine decanoate and fluphenazine plasma levels up to 13 days, a t least, after i.m. single dose (10 mg/kg).