Characterization of quinidine 3-hydroxylation as a probe for the CYP 3A enzyme using a novel capillary electrophoresis technique

European Journal of Pharmaceutical Sciences

Volumn 16, Issue 4-5, 2002, Pages 265-272

  Bhoopathy, S ^a   Sarkar, M A ^a   Karnes, H T ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Capillary electrophoresis; Direct injection technique; High throughput screening; Quinidine metabolism

Indexed keywords

BIOLOGICAL ORGANS; ELECTROPHORESIS; ENZYMES; FLUORESCENCE; HYDROXYLATION; PARTICLE BEAM INJECTION;

MICROSOMES;

DRUG PRODUCTS;

3 HYDROXYQUINIDINE; CYTOCHROME P450 3A; ENZYME; ERYTHROMYCIN; FLUCONAZOLE; ISOENZYME; KETOCONAZOLE; QUINIDINE; QUINIDINE SULFATE;

ABSORPTION; ANIMAL TISSUE; ARTICLE; CAPILLARY ELECTROPHORESIS; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG HYDROXYLATION; DRUG INHIBITION; FLUORESCENCE; INJECTION; LIVER MICROSOME; MICHAELIS CONSTANT; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BIOLOGICAL MARKERS; CYTOCHROME P-450 CYP3A; ELECTROPHORESIS, CAPILLARY; ENZYME INHIBITORS; ERYTHROMYCIN; FLUCONAZOLE; HYDROXYLATION; KETOCONAZOLE; MICROSOMES, LIVER; OXIDOREDUCTASES, N-DEMETHYLATING; QUINIDINE; RATS; RATS, SPRAGUE-DAWLEY; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY; STEREOISOMERISM;

EID: 0036743377     PISSN: 09280987     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0928-0987(02)00109-4     Document Type: Article

References (18)

1. Bhoopathy S., Sarkar M., Karnes H.T. A direct injection capillary electrophoretic technique for miniaturized high-throughput metabolic screening of the CYP 3A4 enzyme using quinidine as a probe. J. Pharm. Biomed. Anal. 25:2001;721-729.
2. Bhoopathy S., Karnes H.T. Determination of (3S)-3-hydroxyquinidine for metabolism screening experiments using direct injection capillary electrophoresis and laser-induced fluorescence detection. Biomed. Chromatogr. 15:2001;1-6.
3. Chauret N., Tremblay N., Lackman R.L., Gauthier J., Silva J.M., Marois J., Yergey J., Nicoll-Griffith D.A. Description of a 96-well plate assay to measure cytochrome P4503A inhibition in human liver microsomes using a selective fluorescent probe. Anal. Biochem. 276:1999;215-226.
4. Crespi C.L., Miller V.P., Penman B.W. Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450. Anal. Biochem. 248:1997;188-190.
5. Drayer D.E., Restivo K., Reidenberg M.M. Specific determination of quinidine and (3S)-3-hydroxyquinidine in human serum by HPLC. J. Lab. Clin. Med. 90:5 1997;816-822.
6. Eagling V.A., Tjia J.F., Back D.J. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br. J. Clin. Pharmacol. 45:2 1998;107-114.
7. Edstein M.D., Prasitthipayong A., Sabchareon A., Chongsuphajaisiddhi T., Webster H.K. Simultaneous measurement of quinine and quinidine in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography with fluorescence detection. Ther. Drug Monit. 12:1990;493-500.
8. Lin K.H., Lu Y.H. Inhibition and induction of cytochrome P450 and the clinical implications. Clin. Pharmacokinet. 35:5 1998;361-390.
9. Meyer U.A. Overview of enzymes of drug metabolism. J. Pharmacokinet. Biopharm. 24:1996;449-459.
10. Mohammed A.L., Hassan M.A., Farid J.M. Analytical Profiles of Drug Substances. Vol. 21: 1983;484-536 Academic Press New York.
11. Nielsen F., Nielsen K.K., Brosen K. Determination of quinidine, dihydroquinidine, (3S)-3-hydroxyquinidine and quinidine N-oxide in plasma and urine by high-performance liquid chromatography. J. Chromatogr. B. 660:1 1994;103-110.
12. Nielsen T.L., Rasmussen B.B., Flinois J., Beaune P., Brosen K. In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. J. Pharmacol. Exp. Ther. 289:1999;31-37.
13. Rodrigues A.D. Preclinical drug metabolism in the age of high-throughput screening: an industrial perspective. Pharm. Res. 14:1997;1504-1510.
14. Rodrigues A.D. Use of in vitro human metabolism studies in drug development: an industrial perspective. Biochem. Pharmacol. 48:1994;2147-2156.
15. Sarkar M., Polk R.E., Guzelian P.S., Hunt C., Karnes H.T. In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes. Antimicrob. Agents Chemother. 34:4 1990;594-599.
16. Segel I.H. Biochemical Calculations. 1976;Wiley New York.
17. Wilkinson G.R. Cytochrome P4503A (CYP3A) metabolism: prediction of in vivo activity in humans. J. Pharmacokinet. Biopharm. 24:5 1996;475-490.
18. Yin H., Racha J., Li S.Y., Olejnik N., Satoh H., Moore D. Automated high throughput human CYP isoform activity assay using SPE-LC/MS method: application in CYP inhibition evaluation. Xenobiotica. 30:2 2000;141-154.