DETERMINATION OF 2 CI-1007 SULFATE METABOLITES IN MONKEY PLASMA AND URINE

Two HPLC assays were developed and validated for simultaneous quantita tion of two sulfate metabolites, PD 163637 (VI) and PD 163639 (VIII), of an investigational antipsychotic drug CI-1007 (I) in monkey plasma and urine. VI and VIII were identified as major metabolites in monkey plasma, and both were excreted in urine. Monkey plasma samples were di rectly injected after deproteinization, and urine samples were analyze d after a clean-up procedure using methyl-tert.-butyl ether. Liquid ch romatographic separation was achieved on a Zorbax RX C-8 analytical co lumn using gradient elution. Column effluent was monitored using fluor escence detection with excitation and emission wavelengths of 254 and 330 nm, respectively. Minimum quantitation limit was 50 ng/ml in plasm a and 100 ng/ml in urine. Linearity was demonstrated up to 3000 ng/ml in plasma and urine. Recoveries of the analytes from plasma and urine were greater than 85%. The assay has been applied to the determination of VI and VIII in plasma and urine samples from monkeys receiving ora l administration of I.