Medicinal Use and Abuse
Benzodiazepines are among the most widely prescribed drugs in the Western world. They are used as anti-anxiety agents, sedative-hypnotics, muscle relaxants, and anticonvulsants. More than 2 dozen different benzodiazepines, ranging from ultra-short acting to long-acting, are available by prescription in the United States.
Despite the relatively high potential for abuse of benzodiazepines, toxicity is comparatively rare. Over dosage produces effects similar to ethyl alcohol intoxication, including drowsiness, ataxia, dysphoria, hypnosis, reduced reflexes, confusions and corns. It is unusual for even a severe benzodiazepine overdose to cause death. Deaths involving benzodiazepines are usually reported when they are taken together with other depressants, such as ethyl alcohol.
Metabolism and Analytical Issues
Benzodiazepines can be present in the urine as parent drug and dealkylated, hydroxylated, and conjugated metabolizes. Detection times for benzodiazepines in urine are extremely variable. Long-acting benzodiazepines (diazepam, nordiazepam, chlordiazepoxide, oxazeparn) are given in large doses and can be detectable in the urine for weeks to months after chronic use. Short-acting benzodiazepines, alprazolam, triazolam) might only be detected for a few days.
Most immunoassays are directed to several benzodiazepines, including Oxazepam and nordiazepam. However, most benzodiazepine immunoassays demonstrate excellent cross reactivity to other benzodiazepines as well. Laboratories will usually calibrate the benzodiazepine immunoassay with either 200 or 300 ng/mL oxazeparn or nordiazepam Because of the large number of benzodiazepines, the confirmation test becomes a critical component in the testing process. Laboratories use GC-MS, LC-MS, or LC-MS-MS for confirmation. Most confirmation testing at a minimum detects oxazepam, nordiazepam, temazepam, a-hydroxyalprazolam, and diazepam. Typically, cutoff concentrations are between 50 and 300 ng/mL. Other benzodiazepines that are not metabolized to these compounds are less frequently included in confirmation tests. As a result, drugs such as flurazepam, lorazepam, clonazepam, and triazolam are often not reported. Because short-acting benzodiazepines are rapidly metabolized to inactive metabolites, detection times are limited. Low dosages typically prescribed for many benzodiazepines and low urinary concentrations of metabolites make benzodiazepine confirmation technically difficult. The MRO needs to know which benzodiazepines are assayed by a particular laboratory, what the cutoff concentrations are, and which analytes are detected in confirmation analyses. Some of the more commonly prescribed benzodiazepines and their urinary metabolites are provided in Table 15.4.
Several nonprescription benzodiazepine-containing products are produced outside the United States. These primary Asian herbal products are often sold in health food stores and vitamin shops and have been found to contain diazepam and lorazepam.