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Test Code VALPF Valproic Acid, Free, Serum

Useful For

Monitoring free valproic acid in therapy

 

Assessing compliance

 

Evaluating potential toxicity

Method Name

Ultrafiltration Followed by Immunoassay

Reporting Name

Valproic Acid, Free, S

Specimen Type

Serum


Specimen Required


Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 2 mL

Collection Instructions:

1. Serum gel tubes should be centrifuged within 2 hours of collection.

2. Red-top tubes should be centrifuged, and the serum aliquoted into a plastic vial within 2 hours of collection.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
  Frozen  28 days
  Ambient  72 hours

Reject Due To

Gross hemolysis Reject

Clinical Information

Valproate (valproate, Depakote, or Depakene) is an effective medication for absence seizures, generalized tonic-clonic seizures, and partial seizures, when administered alone or in conjunction with other antiepileptic agents.

 

The valproic acid that circulates in blood is 85% to 90% protein-bound under normal circumstances. In uremia or during concomitant therapy with other drugs that are highly protein-bound (such as phenytoin), valproic acid is displaced from protein, resulting in a higher free fraction of the drug circulating in blood.

 

Since neurologic activity and toxicity of valproic acid are directly related to the unbound fraction of drug, adjustment of dosage based on knowledge of the free valproic acid concentration may be useful in the following: concomitant use of highly protein-bound drugs (usually >80% bound), hypoalbuminemia, pregnancy, kidney or liver failure, and in older adults. In these situations, the total valproic acid concentration in the blood may underestimate the disproportionately higher free valproic acid fraction.

Reference Values

Therapeutic: 5-25 mcg/mL

Critical value: >30 mcg/mL

Interpretation

The generally acceptable range for total valproic acid used as a reference to guide therapy is 50 to 125 mcg/mL. The corresponding range of free valproic acid concentration for clinical reference is 5 to 25 mcg/mL.

 

Low free valproic acid concentration relative to these ranges may suggest inadequate dosing, whereas a high free valproic acid concentration may be associated with toxic effects.

 

Because the concentration of valproic acid fluctuates considerably depending on the time from last dose, interpretation of the clinical significance of the valproic acid concentration must take into consideration the timing of the blood specimen. For this reason, 2 collections are sometimes made to assess the trough and peak concentrations.

Cautions

Specimens subjected to significant heat or other factors that could cause protein denaturation would demonstrate an artificially increased free valproic acid.

Method Description

The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of valproic acid (free and protein-bound) in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PD) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD+) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PD does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.(Package insert: Valproic acid reagent. Roche Diagnostics; 04/2018)

Day(s) Performed

Monday through Sunday

Report Available

Same day/1 day

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test has been modified from the manufacturer's instructions. Its performance characteristics were 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.

CPT Code Information

80165

LOINC Code Information

Test ID Test Order Name Order LOINC Value
VALPF Valproic Acid, Free, S 4087-3

 

Result ID Test Result Name Result LOINC Value
VALPF Valproic Acid, Free, S 4087-3