A high-throughput assay using liquid chromatography-tandem mass spectrometry for simultaneous in vivo phenotyping of 5 major cytochrome p450 enzymes in patients

Ghassabian, Sussan, Chetty, Manoranjenni, Tattam, Bruce N., Glen, John, Rahme, Jeannie, Stankovic, Zvijezdana, Ramzan, Iqbal, Murray, Michael and McLachlan, Andrew J. (2009) A high-throughput assay using liquid chromatography-tandem mass spectrometry for simultaneous in vivo phenotyping of 5 major cytochrome p450 enzymes in patients. Therapeutic Drug Monitoring, 31 2: 239-246. doi:10.1097/FTD.0b013e318197e1bf


Author Ghassabian, Sussan
Chetty, Manoranjenni
Tattam, Bruce N.
Glen, John
Rahme, Jeannie
Stankovic, Zvijezdana
Ramzan, Iqbal
Murray, Michael
McLachlan, Andrew J.
Title A high-throughput assay using liquid chromatography-tandem mass spectrometry for simultaneous in vivo phenotyping of 5 major cytochrome p450 enzymes in patients
Language of Title eng
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
Language of Journal Name eng
ISSN 0163-4356
1536-3694
Publication date 2009-04-01
Sub-type Article (original research)
DOI 10.1097/FTD.0b013e318197e1bf
Volume 31
Issue 2
Start page 239
End page 246
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Abstract The phenotyping cocktail is a practical approach for phenotyping of cytochrome P450 (CYP) enzymes in vivo. In this study, a liquid chromatography-tandem mass spectrometry method using a dual-extraction approach was developed and validated to quantify 5 selective substrates and their metabolites for the simultaneous phenotyping CYPs 1A2, 2C19, 2C9, 2D6, and 3A4 in patient blood samples. The assay was applied in a pilot study of 11 patients with schizophrenia. Five blood samples were collected before and at 1, 2, 4, and 6 hours after administration of a phenotyping cocktail consisting of 100 mg caffeine, 20 mg omeprazole, 25 mg losartan, 30 mg dextromethorphan, and 2 mg midazolam. The method successfully quantitated the CYP enzyme activities without serious side effects in patients. The ratios of metabolite to parent area under the concentration-time curve values were calculated over the 6-hour postdosage to reflect CYP2D6, CYP3A4, and CYP2C9 activities. The ratios of metabolite to parent plasma concentrations were calculated at 4-hour postdosage for CYP1A2 and at 4- or 6-hour postdose for CYP2C19, respectively. The plasma concentration of midazolam at 4 hours was also estimated as another phenotyping index for CYP3A4 activity. The simultaneous assay of all these analytes in a single matrix (plasma) will increase the feasibility of CYP phenotyping in patients.
Keyword Phenotyping cocktail
Cytochrome P450 activity
LC/MS/MS
Mass spectrometry
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
Centre for Integrated Preclinical Drug Development Publications
 
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Created: Sat, 03 Mar 2012, 02:01:34 EST by Ian Sawyer on behalf of Centre for Integrated Preclinical Drug Development