Objectives Total plasma levels of valproic acid (VPA) may mask an increased risk of adverse effects in hypoalbuminaemic patients since, in these patients, the free fraction is higher. The aim of this study is to analyse the relationship between plasma levels of total and free VPA (_FVPA) in hypoalbuminaemic patients and define an equation that allows the estimation of _FVPA concentration, as well as to validate the obtained equation.

Methods This is a retrospective observational study conducted between January 2015 and January 2020. Hypoalbuminaemic adult patients with normal renal function were included. Serum VPA levels were determined using an automated enzyme immunoassay technique with a pre-treatment of the sample by ultrafiltration for the quantification of _FVPA. Patients’ determinations were randomised into two groups: first, to calculate the _FVPA estimation equation (regression group) by multiple linear regression analysis; and second to validate the equation (validation group), calculating the agreement between experimental and estimated _FVPA concentrations using Lin’s coefficient and a Bland and Altman analysis.

Results We included 51 determinations, corresponding to 33 patients: 26 in the regression group, and 25 in the validation group. The multiple linear regression analysis showed a statistically significant relationship between _FVPA concentration (Y), total VPA concentration (X₁) and albumin level (X₂), explained by the equation Y=11.882 + 0.216*X₁–4.722*X₂. Pearson’s correlation coefficient was 0.798 (p<0.001). Lin’s coefficient was 0.82 (95% CI 0.63 to 0.92). The Bland and Altman analysis showed a bias of 0.32 mg/L, and the concordance limits were between −3.80 and 4.44.

Conclusions The calculated equation adequately predicts _FVPA concentration, with a high degree of correlation between the variables. Despite Lin’s coefficient outcome, Bland and Altman analysis showed a minimum bias that slightly underestimates _FVPA concentration, positioning the calculated equation as a useful and validated estimation tool in hypoalbuminaemic patients with normal renal function.