Calculator inputs
Enter the laboratory values exactly as reported. Select the sample timing and conditions that may alter protein binding.
Formula used
Hermida–Tutor normalization:
CN is the albumin-normalized total valproic acid concentration. CH is the measured total concentration. αH is the albumin-specific free fraction from the published table. The denominator 6.5 represents the table’s free fraction at albumin 42 g/L.
Measured free fraction: measured free VPA ÷ measured total VPA × 100. The tool uses linear interpolation when albumin falls between whole-number entries in the 18–42 g/L table.
The original study found reasonable agreement mainly for total concentrations below about 75 mg/L. The equation may underestimate exposure at higher concentrations because valproate binding is saturable and concentration dependent.
How to use this calculator
- Enter the measured total valproic acid and select its unit.
- Enter serum albumin from the same clinical period and select g/dL or g/L.
- Select the correction method and identify the sample timing.
- Add a measured free concentration when available.
- Choose the laboratory reference range or enter custom limits.
- Select conditions that can alter protein binding.
- Review every caution before using the estimate in clinical discussion.
For the best comparison with the Hermida–Tutor study, use a steady-state trough sample in an adult aged 25–55 years, albumin 18–41 g/L, and total concentration below 75 mcg/mL. Even within those conditions, the result remains an approximation.
Example data
| Scenario | Total VPA | Albumin | Purpose |
|---|---|---|---|
| Near-normal albumin | 65 mcg/mL | 4.0 g/dL | Shows a relatively small correction. |
| Moderate hypoalbuminemia | 55 mcg/mL | 2.8 g/dL | Demonstrates a higher estimated free fraction. |
| Severe hypoalbuminemia | 45 mcg/mL | 1.9 g/dL | Produces a prominent caution despite table coverage. |
| High total concentration | 95 mcg/mL | 3.0 g/dL | Triggers the concentration-dependent binding warning. |
| Measured-free comparison | 60 mcg/mL | 2.5 g/dL | Add free VPA 18 mcg/mL to compare estimate and assay. |
| Outside model range | 50 mcg/mL | 1.5 g/dL | Hermida table result is withheld; direct testing is preferred. |
Clinical meaning and limitations
Valproate binds extensively to albumin, but the relationship is not fixed. Lower albumin can increase the unbound percentage. Higher total concentrations can also saturate binding sites. Therefore, total concentration alone may provide an incomplete view of active exposure.
The correction estimates what total concentration might correspond to a normal-albumin free fraction. It does not prove that a patient has toxicity. Symptoms, indication, timing, dosage form, adherence, organ function, interacting medicines, and the laboratory method remain important. A measured free concentration is preferred when the calculated result conflicts with the clinical picture.
The Hermida–Tutor method was developed in a limited adult seizure population. Its table spans albumin 18–42 g/L. The most favorable agreement occurred below approximately 75 mg/L total valproate. Uremia, bilirubin, salicylates, critical illness, pregnancy, aging, hyperlipidemia, and severe organ disease can create free fractions not predicted by albumin alone.
Reference intervals also differ among laboratories. This page offers selectable presets but allows custom limits. A range describes an assay interpretation framework, not a universal target. Treatment decisions require a clinician who can evaluate benefits, adverse effects, laboratory trends, and the full medication record.
Calculation history
Stored only in this browser using local storage.
| Date | Total | Albumin | Method | Normalized total | Estimated free | Measured free |
|---|---|---|---|---|---|---|
| No saved calculations yet. | ||||||
Frequently asked questions
What does albumin correction estimate?
It estimates an albumin-normalized total concentration and an expected free concentration. Both are approximations based on population binding data.
Is the corrected result the same as a measured free level?
No. A measured free assay directly quantifies unbound valproate. An equation cannot fully capture displacement, organ failure, critical illness, or saturable binding.
Why can total valproate appear normal during toxicity?
A larger portion may be unbound when albumin is low or binding is disrupted. Total concentration can remain ordinary while active exposure rises.
Why does sample timing matter?
The original normalization study used predose trough samples at steady state. Peak or random samples may reflect different concentration phases.
Can this calculator recommend a dose change?
No. It intentionally provides no dose recommendation. Dosing requires clinical assessment, indication-specific goals, adverse-effect review, and laboratory trends.
What happens below albumin 1.8 g/dL?
The Hermida table does not cover that value. The table-based result is withheld because extrapolation could create misleading precision.
Are mg/L and mcg/mL equivalent?
Yes. Their numerical values are equal because one milligram per liter equals one microgram per milliliter.
How are µmol/L values converted?
The tool uses an approximate valproic acid molecular weight of 144.21 g/mol. Laboratory conventions may differ slightly.
Why are several free therapeutic ranges available?
Laboratories publish different assay intervals. Always use the range printed by the laboratory that performed the test when possible.
When is direct free testing especially useful?
It is useful with hypoalbuminemia, renal or hepatic disease, critical illness, pregnancy, suspected toxicity, interacting medicines, or discordant symptoms and total levels.
Does a high corrected value prove toxicity?
No. It signals a need for careful review. Clinical findings and a measured free concentration are more important than a calculated value alone.
Methodology and sources
- Hermida J, Tutor JC. A Theoretical Method for Normalizing Total Serum Valproic Acid Concentration in Hypoalbuminemic Patients. Journal of Pharmacological Sciences. 2005;97:489–493.
- U.S. prescribing information for valproic acid: concentration-dependent protein binding and conditions associated with higher free fractions.
- Mayo Clinic Laboratories: commonly listed total range 50–125 mcg/mL and free range 5–25 mcg/mL.
- ARUP Laboratories: total 50–125 mcg/mL, free 7–23 mcg/mL, and percent free 5–18%; toxic thresholds are laboratory-specific.
Equation version reviewed: July 20, 2026. Confirm current laboratory ranges and product labeling before clinical use.