Navigation Links
Simultaneous Detection of CYP3A4, CYP2D6 and CYP2C9 Metabolites with a Single, Sensitive, LC/MS/MS Method

Jason S. Wood, Varian, Inc.

Introduction

Cytochrome P450s (CYPs) are heme-containing enzymes responsible for initial metabolism of xenobiotics within the human body1. CYPs are part of the Phase I (oxidative) metabolism within the body, which introduces a hydrophilic site on the metabolized drug enabling either easy elimination of the drug or further conjugation by Phase II enzymes, such as UDPGTs, sulfotransferases or amino acid-conjugation (among others)2. Recently there has been increased interest in understanding CYPs to discover the underlying mechanisms of drug-drug interactions3, drug side effect(s)4 and toxicity (including hepatotoxicity). Also relevant to CYP testing is the discovery that polymorphisms in the genetic sequences expressing these enzymes leads to populations of people whose ability to metabolize certain classes of drugs may be attenuated in comparison to other races/populations5.

In this application note LC-ESI-MS/MS is used to simultaneously characterize three drug metabolites for the detection of three different cytochrome P450s enzymatic activities; the hydroxylation of midazolam (CYP3A4), hydroxylation of tolbutamide (CYP2C9) and Odemethylation of dextromethorphan (CYP2D6), see Figure 1. This assay could be used to analyze CYP3A4, CYP2D6 and CYP2C9 activity in vitro for kinetic studies (e.g., liver microsome inhibition studies) or possibly for detection of these metabolites in more complex matrices (plasma or urine) after SPE.

Instrumentation

Varian ProStar 210 Solvent Delivery Modules (2)

Varian 1200L LC/MS equipped with an ESI source

Varian ProStar 430 AutoSampler

Materials and Reagents

All chemicals were reagent or HPLC grade from Sigma- Aldrich Corporation (St. Lo
'"/>

Source:


Page: All 1 2 3

Related biology technology :

1. Simultaneous Detection of 8 Cytokines in Mouse or Human Sera
2. Simultaneous Determination of Residues of Approximately 100 Pesticides and Metabolites in Fruit and Vegetables by LC/MS/MS
3. Simultaneously characterizing and quantifying chloramphenicol and its metabolite using LC/MS/MS
4. Simultaneous Screening of 23 Drugs of Abuse in Oral Fluid Using an LC/MS/MS Method
5. Simple, Sensitive, and Rapid Detection of FLAG -Tagged Fusion Proteins
6. A New PCR-based Mycoplasma Detection Method
7. HSVision Molecular Beacon Detection Module Rapidly Detects Herpes Simplex Virus DNA
8. Detection and Identification of Phosphorylation Sites in Proteins Using LC/MS/MS with Neutral Fragment Loss Mapping
9. Detection of mRNAs on Cryosections of the Cardiovascular System Using DIG-Labeled RNA Probes
10. Gene Expression Arrays: Highly Sensitive Detection of Expression Patterns with Improved Tools for Target Amplification
11. The DIG System Nonradioactive and Highly Sensitive Detection of Nucleic Acids
Post Your Comments:
(Date:9/2/2014)... Sept. 2, 2014  Synthetic Biologics, Inc. (NYSE ... and drug candidates targeting specific pathogens that cause ... from its final preclinical toxicology study of SYN-004. ... this bridging study was required to move the ... prevent the devastating effects of Clostridium difficile ...
(Date:9/2/2014)... /PRNewswire/ - BIOREM Inc. (TSXV: BRM) ("Biorem" or "the Company") today ... of three large odour control systems for waste water treatment ... orders are consistent with the market resurgence in ... and CEO. "After a difficult period of restraint in our ... see sales growth. Our lower cost structure, technology improvements and ...
(Date:9/2/2014)... September 02, 2014 PMG Research, ... 11th clinical research site: PMG Research of Rocky Mount. ... operation of the clinical research department at Boice-Willis ... presence in eastern North Carolina. This new site enhances ... patients in Rocky Mount and the surrounding communities, this ...
(Date:9/2/2014)... Sept. 2, 2014  Spherix Incorporated (SPEX) -- an intellectual property ... intellectual property, today announced that the United States Patent ... Company in the month of August that are part ... The issued patents are: , ... August 19, 2014; and , U.S.RE45,095 issued August ...
Breaking Biology Technology:Synthetic Biologics to Initiate Clinical Trials of SYN-004 in 4Q 2014 to Prevent Potentially Deadly C. difficile Infections 2Synthetic Biologics to Initiate Clinical Trials of SYN-004 in 4Q 2014 to Prevent Potentially Deadly C. difficile Infections 3Synthetic Biologics to Initiate Clinical Trials of SYN-004 in 4Q 2014 to Prevent Potentially Deadly C. difficile Infections 4Synthetic Biologics to Initiate Clinical Trials of SYN-004 in 4Q 2014 to Prevent Potentially Deadly C. difficile Infections 5PMG Research Announces the Formation of its Eleventh Site 2PMG Research Announces the Formation of its Eleventh Site 3United States Patent & Trademark Office Issues Three New Standard Essential Patents to Spherix 2
... Databases ... Receptors and Proteases, PARIS, August 18 Aureus ... life sciences discovery,announced today the release of three new ... for the important,drug targets Nuclear Receptor and Protease, as ...
... Aug. 18 LifeVantage Corporation,(OTC Bulletin Board: LFVN), the ... the progressive rate of aging, today announced,that the company,s ... interview on WallSt.net,s 3-Minute Press Show., The interview ... of the company,s latest press release., ...
... Inc. (OTC Bulletin Board: YGYB) ("Yongye" or the "Company"),a ... and,animals in the People,s Republic of China, today announced ... Second Quarter 2008 Highlights -- Revenue ... second quarter of 2007, and ...
Cached Biology Technology:Aureus Pharma Releases New Unified Knowledge Database 2[video] David Brown, President and CEO of LifeVantage Corporation, Discusses Record Page Views on WallSt.net's 3-Minute Press Show 2Yongye Biotechnology International Announces Second Quarter Results 2Yongye Biotechnology International Announces Second Quarter Results 3Yongye Biotechnology International Announces Second Quarter Results 4Yongye Biotechnology International Announces Second Quarter Results 5Yongye Biotechnology International Announces Second Quarter Results 6Yongye Biotechnology International Announces Second Quarter Results 7Yongye Biotechnology International Announces Second Quarter Results 8Yongye Biotechnology International Announces Second Quarter Results 9Yongye Biotechnology International Announces Second Quarter Results 10Yongye Biotechnology International Announces Second Quarter Results 11
(Date:9/2/2014)... and their propensity for eating anything, including each other, ... research from North Carolina State University finds that non-native ... eastern United States. , "The good news is that ... threat to humans," says Dr. Mary Jane Epps, a ... a paper about the research. , The research stems ...
(Date:9/2/2014)... Tithonian Konservat-Lagersttte of lithographic limestone is well known ... fossils from that area (for example, Archaeopteryx). Now, ... insects in the French equivalent of these outcrops ... the oldest known water treader. , Despite the ... fewer fossils have been obtained from the Late ...
(Date:9/2/2014)... DURHAM, N.C. -- When you accidentally touch a hot ... know the basic neural circuits involved in sensing and ... out the molecular players. , Duke researchers have made ... molecule involved in pain in worms, and have built ... Sept. 2 in Nature Communications , may help ...
Breaking Biology News(10 mins):Researchers find Asian camel crickets now common in US homes 2Exceptionally well preserved insect fossils from the Rhône Valley 2Surprising new role for calcium in sensing pain 2Surprising new role for calcium in sensing pain 3
... the Johns Hopkins School of Medicine and their colleagues have ... addition to their own can acquire new color vision, a ... new sensory information than anticipated. , This work, appearing ... ancestral primate inherited a new type of photoreceptor more than ...
... aren't as busy as, well, a bee. It all ... that a key to the insects' success in adapting to ... temperatures when flying to flowers. Whether and how they ... from the University of Washington and the University of Puget ...
... Schulich School of Medicine & Dentistry at The University ... Edinburgh, have discovered a way to kill the cystic ... of Dr. Miguel Valvano, Department of Microbiology and Immunology, ... of the Journal of Bacteriology, and highlighted in Nature ...
Cached Biology News:Making mice with enhanced color vision 2Making mice with enhanced color vision 3Bumblebee house warming -- it takes a village 2Bumblebee house warming -- it takes a village 3Key found to kill cystic fibrosis superbug 2
Rabbit polyclonal to Somatostatin 28 ( Abpromise for all tested applications). entrezGeneID: 6750 SwissProtID: P61278...
... Features Convenient platform for tube ... - 96 x 0.2ml V-bottom tubes ... Thermo-Tube Plates - Thermo-Fast® 96 Non-Skirted ... - 48 x 0.5ml Thermo-Tubes Multiple ...
... Pro upgrade for Shimadzu Phoretix 2D, Expression ... statistical tools for comparative gel analysis studies ... Data base add on component ... version 9i release 2 client software). ...
... systems provide linking and labelling reagents ... specific primary antibodies for visualising cellular ... accomplished using an ultra-sensitive indirect labelling ... technology. Secondary antibodies are polymerised directly ...
Biology Products: