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Background and Importance Valproic acid (VA) binds strongly to albumin. In hypoalbuminaemia, the free valproic acid fraction (FVPA) – the pharmacologically active form – increases, raising efficacy and toxicity risks. Determining FVPA concentration is therefore crucial for monitoring, dose adjustment, and treatment safety.Aim and Objectives The primary objective was to evaluate the influence of hypoalbuminaemia on the relationship between total VA and FVPA concentrations. Secondarily, a proposed formula for the theoretical calculation of FVPA was compared with measured values. 1 Material and Methods Retrospective and descriptive study was conducted on patients treated with VA, between January 2024 and September 2025 at a tertiary hospital.Data were extracted from Orion Clinic and Gestlab systems, including demographic (sex, age), anthropometric (weight, height), and biochemical parameters (VA, FVPA, albumin, and total proteins). Patients were classified as normoalbuminaemic (≥ 3.5 g/dL), mildly hypoalbuminaemic (2.5–3.4 g/dL), or severely hypoalbuminaemic (< 2.5 g/dL).According to the literature, a target therapeutic range was established at 5-15 mcg/mL and 50-10 mcg/mL for FVPA and VA, respectively.Results A total of 31 patients were included, 65% women, with an average age of 58 ± 17 years. Distribution by albumin status was 61.5% (19) normal, 32% (10) mild, and 6.5% (2) severe hypoalbuminaemia, analysing a total of 48 samples.Regarding FVPA concentration, supratherapeutic levels were observed in 41.9% (13) of patients, 69.2% (9) of whom were hypoalbuminaemic – 53.8% (7) mildly and 15.4% (2) severely. Notably, several patients exhibited FVPA levels above the therapeutic range despite total VA concentrations within or below the recommended range. 30.8% (4) had total VA concentrations at the lower limit or subtherapeutic range.Comparison of measured FVPA concentrations versus the ones calculated with the proposed formula revealed a mean difference of 4.96%.Conclusion and Relevance More than half of the patients with supratherapeutic FVPA concentrations were hypoalbuminaemic, often with total VA below the target range. All cases of severe hypoalbuminaemia showed elevated FVPA concentrations. These results underscore the importance of directly measuring FVPA in hypoalbuminaemic patients to optimise dosing, clinical interpretation and prevent toxicity.References and/or Acknowledgements 1. Pretorius E, van Zyl P, Joubert G. Therapeutic drug monitoring for valproate: deriving a novel formula for calculation of free concentration. Eur J Clin Pharmacol. 2024;80(11):1751–9. doi:10.1007/s00228-024-03741-2Conflict of Interest No conflict of interest