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Abstract

Fenfluramine hydrochloride has recently attracted international attention owing to its marked antiseizure effects, even in refractory epilepsy. In pediatric practice, however, very small doses are often required, and the high viscosity of the oral solution, together with its inability to mix with foods or beverages, can lead to drug loss during administration. Although rinsing oral administration pipette with a small amount of water may help to ensure accurate dosing, the effects of dilution on formulation stability and impurity formation remain to be clarified. To address this gap, we examined the stability of fenfluramine after dilution in purified water. The diluted fenfluramine hydrochloride oral solution was analyzed via liquid chromatography–mass spectrometry. Component analysis was performed using an ACQUITY ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry system (Waters, Milford, MA) in scan mode with positive electrospray ionization over an m/z range of 50 1200. For analysis, 100 µL of fenfluramine hydrochloride oral solution was diluted in 10 mL of purified water or methanol and then diluted 10,000-fold before measurement. The base peak intensity chromatograms reveal a clear peak corresponding to the main component immediately after dilution and 24 h later, with no change in the mass spectrum. The detected ion is consistent with C12H16NF3 from fenfluramine. The formulation stability of fenfluramine hydrochloride was no apparent change in the main LC/MS signal, thus which may therefore a practical method for ensuring accurate dosing. Further, this implies that even when small amount of residual fenfluramine hydrochloride solution must be administered in a little water, the drug will remain stable, thus contributing to effective treatment. A case study of the administration of fenfluramine hydrochloride to a nine-year-old girl with Dravet Syndrome is presented.

Keywords: Fenfluramine hydrochloride, Dravet syndrome, Medication administration support, Purified water, Dilution stability