High performance liquid chromatography method validation for identification and quantification of valproic acid in oral solutions: Monitoring of products marketed in Argentina (2022)

Abstract

Valproic acid (VPA) is one of the first-line drugs for the treatment of epilepsy, one of the most prevalent neurological disorders, in adults and children. It is classified as an active ingredient with a narrow therapeutic range, which implies that its effective and safe use requires careful dosing and patient monitoring. The main severe adverse effects include hepatotoxicity and pancreatitis, which can be fatal, being especially susceptible children under two years of age and older adults. Currently, the quantification assay for VPA in oral solution codified in the Argentine National Pharmacopoeia (FNA) is by gas chromatography (GC), which involves greater complexity in sample preparation and is less accessible than liquid chromatography. The objective of this work was to validate a high performance liquid chromatography methodology (HPLC) for the identification and quantification of VPA solutions. Once the technique was validated, the analysis of all products marketed in Argentina was carried out, and the quality control techniques used by the manufacturing laboratories were evaluated. The samples analysed were within specification, while corrective actions emerged from the evaluation of the documentation and were indicated to the laboratories. This technique allows for a quick, simple and more applicable analysis, which could be established as a control standard in the FNA.