Published: Journal of Analytical Toxicology, Volume 22, Number 7, November/December 1998, pp. 559-566
Benzodiazepines: Toxic Serum Concentrations in Positive Enzyme
Immunoassay Responses
F. Divanon, D. Debruyne, M. Moulin, and R. Leroyer
A total of 588 blood specimens collected in an emergency unit were screened
for benzodiazepines (BZDs) using
enzyme-multiplied immunoassay and gas chromatography. Two-hundred eighty-five
samples were positive for BZDs, and 303 samples that were negative by EMIT®
included 20 samples with BZDs detectable by gas–liquid chromatography.
A total of 15 BZDs were identified, and the most frequently occurring were nordiazepam,
bromazepam, diazepam, and alprazolam. Individual BZDs were found in 74% of cases,
but some samples contained two, three, or even four BZDs. There is a risk of
missing intoxication by BZDs with low therapeutic range and/or low
cross-reactivity (alprazolam, bromazepam, flunitrazepam). There is a risk of
misinterpreting a positive result for some BZDs with high therapeutic range
and/or high cross-reactivity (nordiazepam), which may reflect a pharmacologically
ineffective concentration. A semiquantitative analysis is inappropriate even
when the identity of BZD is known. Immunoassays are the only methods presently
available for use in emergencies, but physicians must be clearly informed of
their limitations and interpret results with caution.
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