Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-25
pubmed:abstractText
Dextromethorphan (DEM) is a widely used probe drug for human cytochrome P450 2D6 isozyme activity assessment by measuring the ratio between DEM and its N-demethylated metabolite dextrorphan (DOR). DOR is excreted in urine mainly conjugated to glucuronic acid. Prior to quantification, DOR must be deconjugated to avoid variability caused by the polymorphic glucuronosyltransferase enzyme. A chemical hydrolysis method was optimized using a chemometric approach. Three factors (acid concentration, hydrolysis time and temperature) were selected and simultaneously varied to study their effect on conjugated DOR hydrolysis. Hydrolysis conditions that maximize DOR release without significant degradation of both DEM and DOR were chosen and results were compared to those obtained by enzymatic method using beta-glucuronidase. An HPLC method with fluorescence detection was developed for the simultaneous quantitation of DEM, DOR and levallorphan, used as an internal standard. Separation was performed on a phenyl analytical column (150 mmx4.6 mm i.d., 5 microm) with a mobile phase consisting of 18% acetonitrile and 50 mM phosphoric acid (pH 3). The overall analytical procedure was validated and showed good performances in terms of selectivity, linearity, sensitivity, precision and accuracy. Finally, this assay was used to determine DEM/DOR molar ratios in fibromyalgia patients for the purpose of determining phenotype status for the CYP2D6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1570-0232
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
861
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
56-63
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Development and validation of a chemical hydrolysis method for dextromethorphan and dextrophan determination in urine samples: application to the assessment of CYP2D6 activity in fibromyalgia patients.
pubmed:affiliation
Clinical Pharmacology and Toxicology, Geneva University Hospitals, CH-1211 Geneva 14, Switzerland. youssef.Daali@hcuge.ch
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't