Monitoring chlordiazepoxide therapy
Assessing toxicity
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Benzodiazepines
Librium (Chlordiazepoxide)
Nordiazepam
Serum Red
Supplies: Amber Frosted Tube, 5 mL (T192)
Collection Container/Tube: Red top
Submission Container/Tube: Amber vial
Specimen Volume: 0.5 mL
Collection Instructions: Centrifuge and aliquot serum into amber vial within 2 hours of collection.
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Neurology Specialty Testing Client Test Request (T732)
-Therapeutics Test Request (T831)
0.3 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum Red | Refrigerated (preferred) | 14 days | LIGHT PROTECTED |
Frozen | 14 days | LIGHT PROTECTED | |
Ambient | 24 hours | LIGHT PROTECTED |
Monitoring chlordiazepoxide therapy
Assessing toxicity
Chlordiazepoxide (Librium) is a benzodiazepine widely used in the treatment of anxiety, alcohol withdrawal symptoms, and as a premedication for anesthesia. The mechanism of action of all benzodiazepines remains unclear. However, it is known that benzodiazepines facilitate gamma-amino butyric acid (GABA)-mediated neurotransmission in the brain. Benzodiazepines most likely facilitate the inhibitory presynaptic or postsynaptic reactions of GABA.
Chlordiazepoxide is metabolized to long-acting metabolites in the liver to the active metabolite nordiazepam (desmethyldiazepam) and the clearance of the drug is reduced considerably in the elderly and in patients with hepatic disease.
Therapeutic assessment should include measurement of both the parent drug (chlordiazepoxide) and the active metabolite (nordiazepam).
Since chlordiazepoxide has a wide therapeutic index and toxicity is dose-dependent, routine drug monitoring is not indicated in all patients.
Therapeutic concentration:
Chlordiazepoxide: 400-3,000 ng/mL
Nordiazepam: 100-500 ng/mL
Chlordiazepoxide and nordiazepoxide combined concentrations above 5000 ng/mL have been associated with toxicity.
The specimen must be protected from light.
1. Langman, LJ, Bechtel L, Meier BM, Holstege CP, Clinical toxicology. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:832-887
2. Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. WB Saunders Company; 2011:1109-1188
3. Hiemke C, Baumann P, Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry. 2011;44:195-235
The internal standard mixture containing chlordiazepoxide-d5, diazepam-d4, and nordiazepam-d5 is added to serum samples. The serum samples are treated with phosphate buffer and extracted via liquid/liquid extraction. The organic layer from the extraction is dried under nitrogen, reconstituted, and injected on a liquid chromatography-tandem mass spectrometer (LC-MS/MS).(Unpublished Mayo method)
Monday, Wednesday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
80346
G0480 (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
CDP | Chlordiazepoxide and metabolite, S | 33060-5 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
8610 | Chlordiazepoxide | 3457-9 |
37321 | Nordiazepam | 3537-8 |