Benzodiazepines (part 2) –
Interpreting Laboratory Results
Dr. Joseph E. Graas, Scientific Director
Dr. Edward Moore, Medical Director
It can be very difficult to accurately interpret a Benzodiazepines (Benzo) class result. Very little data can be determined from a screening test alone; in most cases, additional confirmatory testing by GC/MS or LC/MS is required for accurate interpretation.
The Benzo class is vast and complicated; there are 36 compounds that make up the Benzo class. Of those 36, only 20 are approved for use in the USA (for detailed list, see chart in Part 1 of article). With every class screen, there is a target compound. For Benzos, the target compound is Oxazepam. As a separate example, the target compound for the Opiate class is Morphine. In addition, a cutoff level is always referenced. Most Benzo screens (either by onsite device or laboratory) are validated to Oxazepam at 300 ng/mL. What this means is that the target drug will be detected at 100% of its value and at its actual concentration (i.e. a 300 ng/mL solution of Oxazepam will give a positive result at a cutoff of 300 ng/mL).
On a Benzo class screen, the test can respond to the chemical structure that ANY of the drugs in the Benzo category have in common. The test is designed to indicate a positive value in every case where the target compound (Oxazepam) is present at the defined concentration. This means that all true positives must be positive. However, due to the complexity of the testing drug matrix, and considering all of the biological background, some true negative samples will result as positive. There can also be medication cross reactions. The drug test is designed to minimize this false positive, but with the requirement that all true positives must be positive, a certain amount of these false positives are allowed in the screen.
When reviewing class data, compounds other than the target compound may be more or less sensitive to the test. The extreme examples are Xanax (Alprazolam) and Ativan (Lorazepam). A urine concentration of 300 ng/ml of Xanax will give a positive result with an apparent screening concentration of greater than 2500 ng/ml and Ativan at 300 ng/mL will be virtually undetectable by the same test. Klonopin (Clonazepam) at 300 ng/mL will generally yield a screening value lower than the cutoff level. Many treatment programs elect to lower their Benzo screening level to 200 ng/mL in efforts to capture illicit Klonopin use. This is something to take into consideration before lowering a cutoff level. A lower cutoff level will result in more data, but not all the data is useful and can be frustrating.
With the vast variety of Benzos available, both licit and illicit, it is nearly impossible to accurately correlate an immunoassay screening value back to a single Benzo. It is understood within the laboratory community that particular medications generally yield screening results in a certain range for certain medications, but not definitively. For example, a patient taking a Lorazepam source is not expected to trigger a positive result in the screening test; patients taking a Clonazepam source may be positive or may be negative and generally have a screening value around the cutoff level. Patients taking Diazepam or Alprazolam are always expected to yield a positive result.
However, where the danger lies is this: a screening result of 2250 ng/mL for the Benzodiazepines may be from Alprazolam; it also may be from a patient taking a combination Diazepam and Clonazepam; or it could be from Temazepam and Lorazepam. Point being, the combinations are endless. Interpreting an immunoassay value relies on assumptions and generalizations. To definitively interpret a Benzo result, a confirmation test should be performed to accurately identify the individual Benzo analytes present and defined concentrations.