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Mayo Test ID CDP Chlordiazepoxide and Metabolites, Serum


Shipping Instructions


Ship specimen in amber vial to protect from light.



Specimen Required


Supplies: Amber Frosted Tube, 5 mL (T915)

Collection Container/Tube: Red top (serum get/SST are not acceptable)

Submission Container/Tube: Amber vial

Specimen Volume: 1 mL

Collection Instructions: Within 2 hours of collection, centrifuge and aliquot serum into an amber vial.


Useful For

Monitoring chlordiazepoxide therapy

 

Assessing toxicity

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Chlordiazepoxide and metabolites, S

Specimen Type

Serum Red

Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Refrigerated (preferred) 28 days LIGHT PROTECTED
  Ambient  28 days LIGHT PROTECTED
  Frozen  28 days LIGHT PROTECTED

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Clinical Information

Chlordiazepoxide (Librium) is a benzodiazepine widely used in the treatment of anxiety and alcohol withdrawal symptoms, as well 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 metabolites nordiazepam (desmethyldiazepam) and oxazepam, and the clearance of the drug is reduced considerably in older adults and in patients with hepatic disease.

 

Therapeutic assessment should include measurement of both the parent drug (chlordiazepoxide) and the primary active metabolite (nordiazepam), with a proposed combined chlordiazepoxide and nordiazepam reference interval of 700 to 1000 ng/mL. However, therapeutic and toxic concentrations can vary greatly and should be interpreted in the full clinical context of the patient. Since chlordiazepoxide has a wide therapeutic index and toxicity is dose-dependent, routine drug monitoring is not indicated in all patients.

Reference Values

Therapeutic concentration:

Chlordiazepoxide: 400-3,000 ng/mL

 

Cutoff concentrations by liquid chromatography tandem mass spectrometry:

Chlordiazepoxide: 10 ng/mL

Nordiazepam: 10 ng/mL

Oxazepam: 10 ng/mL

Interpretation

Combined concentrations of chlordiazepoxide and nordiazepam above 5000 ng/mL have been associated with toxicity.

Cautions

The specimen must be protected from light.

Clinical Reference

1. Langman LJ, Bechtel LK, Holstege CP. Clinical toxicology. In: Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:chap 43

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, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62

4. Adeli K, Higgins V, Bohn MK. Reference information for the clinical laboratory. In: In: Rifai N, Chiu RWK, Young I, Burnham CAD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023:1390-1470

Method Description

The internal standard mixture containing chlordiazepoxide-d5, diazepam-d5 , nordiazepam-d5, oxazepam-d5, and temazepam-d5 is added to serum samples, mixed, and centrifuged. The supernatant is diluted and injected on a liquid chromatography tandem mass spectrometer.(Unpublished Mayo method)

Day(s) Performed

Wednesday

Report Available

2 to 7 days

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

80299

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CDP Chlordiazepoxide and metabolites, S 33060-5

 

Result ID Test Result Name Result LOINC Value
8610 Chlordiazepoxide 3457-9
37321 Nordiazepam 3537-8
622870 Oxazepam 3886-9