The document describes the metabolism of drugs in the body and the impact of enzyme activity on the formation and excretion rate of metabolites. The CYP3A4 and CYP2D6 enzyme families are considered the most important in this activity. The document uses dextromethorphan as a probe for the activity of the CYP2D6 metabolic phenotype and describes the metabolism and excretion of the drug in different metabolic types of patients. Additionally, the document mentions that some individuals have multiple copies of the gene that produces the CYP2D6 enzymes, leading to high metabolic rates of many drugs in these individuals and rendering the drugs therapeutically ineffective.
The document describes a method for identifying dextromethorphan metabolites in urine using an Agilent LC/MS system. It details the experimental procedure, including sample preparation involving acidification with phosphoric acid and extraction with acetonitrile.
Results show that the Agilent 1100 Series LC/MSD Trap XCT Plus system combined with ACD/Labs version 8 software can rapidly locate differences between samples and controls. The study confirmed the presence of major metabolites such as dextrorphan, dextrorphan glucuronide, and 3-hydroxymorphinan glucuronide.
It illustrates how to use the Agilent 1100 Series LC/MSD Trap XCT Plus system and ACD/Labs version 8 software for metabolism or forensic studies.
A single dose containing 30 mg of dextromethorphan was administered to a healthy male volunteer.