Determination of the Enantiomeric Purity of Solriamfetol by High-Performance Liquid Chromatography in Polar Organic Mode Using Polysaccharide-Type Chiral Stationary Phases

Abstract

Solriamfetol is a novel FDA approved enantiopure drug used for the treatment of excessive sleepiness associated with narcolepsy or obstructive sleep apnea. Only the active R-enantiomer is marketed, therefore, a method to determine the chiral purity is essential. Chiral separation of solriamfetol was performed by HPLC using polysaccharide-type chiral stationary phases in polar organic mode and described for the first time. Seven different polysaccharide-based chiral columns (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2, Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3 and Lux Cellulose-4) were employed for the separation of enantiomers using polar organic mode, with mobile phases consisting of 0.15% diethylamine in methanol (MeOH), 2-propanol (IPA) or acetonitrile (ACN). During the screening phase, the best results (Rs> 5, in less than 10 min) was obtained on a Lux Amylose-1 column with 0.15% diethylamine in methanol with an ideal elution order (the distomer eluted before the R-enantiomer). The effects of binary mobile phases on the resolutions and retention factors were also investigated containing different percentages of MeOH:ACN and MeOH:IPA. Using optimized parameters (Lux Amylose-1 column with 0.05% diethylamine in MeOH with 0.6 mL/min flow rate at 20 °C) high enantioresolution (Rs = 5.3) was achieved within 6 min. Thermodynamic analysis was performed and revealed an enthalpy-driven enantioseparation. The developed, isocratic HPLC method was validated according to current ICH guidelines and proved to be reliable, linear, precise and accurate for the determination of 0.1% S-enantiomer as a chiral impurity in R-solriamfetol.