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 wer...

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Bibliographic Details
Published in:Journal of chromatography. B, Biomedical sciences and applications Biomedical sciences and applications, 1997-05, Vol.693 (1), p.159-166
Main Authors: Feng, M.Rose, Atherton, J, Knoll, S, Strenkoski, Carol A, Wright, D.Scott
Format: Article
Language:English
Subjects:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - analogs & derivatives
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - analysis
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - blood
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - urine
Analysis
Animals
Antipsychotic Agents - analysis
Antipsychotic Agents - blood
Antipsychotic Agents - urine
Benzenesulfonates - analysis
Benzenesulfonates - blood
Benzenesulfonates - urine
Biological and medical sciences
Chromatography, High Pressure Liquid
CI-1007
CI-1007 sulfates
Drug Stability
General pharmacology
Haplorhini
Medical sciences
Pharmacology. Drug treatments
Pyridines - analysis
Pyridines - blood
Pyridines - urine
Sensitivity and Specificity
Spectrometry, Fluorescence
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Summary: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 C 8 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.
ISSN:0378-4347
1387-2273
DOI:10.1016/S0378-4347(97)00015-7