Determination of two CI-1007 sulfate metabolites in monkey plasma and urine.
Two HPLC assays were developed and validated for simultaneous quantitation 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 directly injected after deproteinization, and urine samples were analyzed after a clean-up procedure using methyl-tert.-butyl ether. Liquid chromatographic separation was achieved on a Zorbax RX C8 analytical column using gradient elution. Column effluent was monitored using fluorescence detection with excitation and emission wavelengths of 254 and 330 nm, respectively. Minimum quantitation limit was 50 ng/ml in plasma 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 oral administration of I.
Feng
M R
MR
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Atherton
J
J
Knoll
S
S
Strenkoski
C A
CA
Wright
D S
DS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000652:urine; D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D001557:Benzenesulfonates / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D000882:Haplorhini; D011725:Pyridines / Q000032:analysis* / Q000097:blood / Q000652:urine; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
D014150:Antipsychotic Agents; D001557:Benzenesulfonates; C107214:PD 163637; C107215:PD 163639; D011725:Pyridines; C090025:1,2,3,6-tetrahydro-4-phenyl-1-((3-phenyl-3-cyclohexen-1-yl)methyl)pyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine