Benzodiazepines Drug Information

Classification

Metabolism

The benzodiazepines are well absorbed after oral administration and rapidly distributed throughout the body. They are extensively metabolized by the liver and generally excreted in the urine as- pharmacologically inactive conjugated metabolites. Some metabolites may possess pharmacological activity. Oxazepam, marketed as the drug Serax®, is also a common metabolite of several benzodiazepines such as diazepam and temazepam. The window of detection in urine is varied. Ingestion of therapeutic dosages may be detectable for 1-3 days while extended usage over a period of months or years can extend excretion times up to 4-6 weeks after cessation of use.

Abuse

The benzodiazepines are considered one of the most widely prescribed class of drugs in the United States, thus leading to their widespread abuse. Diazepam (Valium®) and alprazolam (Xanax®) are two of the most widely abused benzodiazepines. Other commonly abused benzodiazepines are clonazepam (Klonopin®) and lorazepam(Ativan®). Many abusers will attempt to accentuate the effects of benzodiazepines by the concomitant use of alcohol or other CNS depressants. Prolonged high doses of benzodiazepines can cause dependency, and a withdrawal syndrome may occur following abrupt cessation of use.

Laboratory drug testing: Methods of Analysis

There are many problems associated with a comprehensive approach to the analysis of the benzodiazepines. The benzodiazepines are a very diverse and complex group of compounds which are extensively metabolized in urine. For this reason, it is not always possible to determine the parent drug with urine testing. In addition, dosage levels vary substantially affecting the ability to detect therapeutic levels.

The most common analytical techniques to screen for the presence of benzodiazepines in urine are immunoassay methods such as enzyme immunoassay (EIA). Immunoassay methods are designed to optimally detect oxazepam, however many other structurally similar benzodiazepines may also be detected.

While immunoassay cross-reactivity to non-benzodiazepine compounds is rare, immunoassay positive results must be confirmed by a specific analytical method such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). It is essential to understand the advantages and limitations of the various laboratory analytical methods to ensure proper detection of benzodiazepines.