Definition
- A class of drugs with a three-ringed chemical structure consisting of a benzene ring, a seven-member diazepine ring, and a phenyl ring attached to the 5-position of the diazepine ring. The CNS depressant activity of these drugs is mediated through the neurotransmitter, GABA.
- Specific agents: alprazolam (Xanax), chlordiazepoxide (Librium), diazepam (Valium), temazepam (Restoril), oxazepam (Serax), flunitrazepam (Rohypnol), lorazepam (Ativan), midazolam (Versed), clonazepam (Klonopin), and triazolam (Halcion).
- Normal range: see Table 16.11.
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TABLE 16 " “11Reference Ranges of BenzodiazepinesView LargeTABLE 16 " “11Reference Ranges of Benzodiazepines Normal Range (serum/plasma; ng/mL) Alprazolam 10 " “100 Chlordiazepoxide 500 " “2,500 Clonazepam 5 " “75 Diazepam 100 " “1,500 (may be higher to control alcohol withdrawal and in schizophrenic patients) Flunitrazepam 10 " “20 Lorazepam 5 " “240 Midazolam 8 " “150 (higher for surgical anesthesia; may be >1,000) Oxazepam 300 " “1,500 Temazepam 200 " “1,200 Triazolam 2 " “10
Use
- Assistance in the treatment of panic attacks, panic disorders, and agoraphobia (alprazolam, clonazepam)
- Treatment of anxiety (diazepam, lorazepam)
- Treatment of seizures (diazepam, clonazepam)
- Treatment of insomnia (temazepam, triazolam)
- Preoperative sedation and to assist in induction of surgical anesthesia (midazolam, diazepam, lorazepam)
- Muscle relaxant (diazepam)
- Treatment of alcohol dependence (chlordiazepoxide, diazepam)
Interpretation
- When evaluating concentrations in plasma/serum, effect of multiple active moieties must be considered. When evaluating concentrations in urine, metabolite rather than parent may be detected. Active metabolites are
- Alprazolam: alpha-hydroxy alprazolam
- Flunitrazepam: 7-aminoflunitrazepam
- Midazolam: alphahydroxy and 4-hydroxy midazolam
- Triazolam: alphahydroxy and 4-hydroxy triazolam
- Diazepam: nordiazepam, temazepam, oxazepam
- Chlordiazepoxide: demoxepam, norchlordiazepoxide, nordiazepam, oxazepam
- Temazepam: oxazepam
Limitations
- Testing: screening by immunoassay for urine and serum
- ELISA (serum)
- Target analyte: temazepam
- Cutoff concentration: 10 ng/mL
- No cross-reactivity with clonazepam, flunitrazepam, lorazepam and metabolites, and oxazepam
- EMIT (serum/urine)
- Target analyte: nitrazepam (urine), diazepam (serum)
- Cutoff concentration: 200 or 300 ng/mL urine, 50 ng/mL serum
- Due to low cross-reactivity, will not detect flunitrazepam, clonazepam, lorazepam (urine); low cross-reactivity with chlordiazepoxide and demoxepam (serum)
- Cross-reactivity with alprazolam manufacturer (vendor) dependent
- Confirmation for urine and serum
- Sample pretreatment necessary
- Derivatization may be necessary for metabolite detection.
- Hydrolysis of urine samples increases detectability.
- Gas chromatography (GC).
- HPLC.
- Low-dose benzodiazepines may not be measurable by GC and HPLC (triazolam, flunitrazepam).
- GC/MS [MS].
- LC/MS/[MS].
- Target drug: parent drug and metabolites.
- Limit of quantitation: typically 5 " “20 ng/mL.