Demystifying Benzodiazepine Urine Drug Screen Results

Demystifying Benzodiazepine Urine Drug Screen Results

It is not uncommon for physicians to prescribe both opioids and benzodiazepines for patients with chronic pain.

When used in conjunction with opioid pain medications, benzodiazepines have been shown to enhance pain relief, but the combination can be accompanied by increased risks for abuse and accidental overdose  


Given the increasing and widespread use of benzodiazepines, both alone and in conjunction with other medications, it is important for clinicians to fully understand a patient’s urine drug screen (UDS) results to support the management of their care.

Table 1 provides a list of generic and brand drug names, parent drug half-life information, and speed of onset for the commonly prescribed benzodiazepines.


Typical detection windows for benzodiazepines in the urine are 2 to 7 days, depending on the individual benzodiazepine drug used and other factors, such as time of last dose, drug half-life, route of administration, and individual differences in pharmacokinetics.

It is beneficial to document the date of the last dose taken by the patient when submitting the sample to aid in UDS interpretations.

Genetic differences in metabolic pathways resulting in fast or slow metabolism also need to be considered when evaluating UDS results.


The flow chart in Figure 1 provides parent drug and metabolites that should be encountered during benzodiazepine metabolism.


Following administration, diazepam undergoes metabolism to yield the active metabolites nordiazepam and temazepam. Nordiazepam and temazepam are then further metabolized to the final active metabolic product oxazepam. Thus, the presence of nordiazepam, temazepam, and oxazepam together on a UDS is consistent with diazepam use

Since clonazepam undergoes metabolism to produce the primary urinary metabolite of 7-aminoclonazepam, the presence of this metabolite is consistent with clonazepam use

Alprazolam is metabolized after administration to the primary urinary metabolite alpha-hydroxyalprazolam. Thus, the presence of alprazolam and/or alpha-hydroxyalprazolam on a UDS would indicate recent alprazolam use

After administration, lorazepam undergoes glucuronidation to produce lorazepam-glucuronide. In a UDS, finding the parent drug lorazepam indicates recent use


The concentrations listed in Table 2 show the lowest levels that yield positive results when using the DRI Benzodiazepine Assay


Due to the probability of obtaining a false negative with the initial IA test for lorazepam and clonazepam, it is important that these compounds be tested via MS for precise drug identification

So, even with a negative result, they are recommending Mass Spec tests, which cost $1500 and are NOT covered by most insurance. Where does it end? comment by Zyp Czyk


Interpretation of benzodiazepine UDS results often is not straightforward due to the complexity of the metabolic pathways of these agents, particularly diazepam, and the potential for limited cross-reactivity of the IA resulting in false negatives (lorazepam and clonazepam). Using a laboratory that understands this complexity will provide the necessary information to evaluate benzodiazepine use in your patients.  


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