LAUSR

R‐solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S‐enantiomer in addition to the enantiomers of its major impurity phenylalaninol. Twenty‐nine different cyclodextrins (CDs), including native, neutral, and charged ones were screened as potential chiral selectors, and the best results were obtained with sulfated CDs. Randomly sulfated‐β‐CD exhibited outstanding enantioresolution, the peaks of phenylalaninol enantiomers inserted between the two peaks of solriamfetol enantiomers, while sulfated‐γ‐CD (S‐γ‐CD) showed remarkable resolution values in a much shorter analysis time with the optimal enantiomer migration order. Among the single isomer sulfated CD derivatives, substituent dependent enantiomer migration order reversal could also be observed in the case of heptakis(6‐O‐sulfo)‐β‐CD (HS‐β‐CD) or heptakis(2,3‐O‐dimethyl‐6‐O‐sulfo)‐β‐CD (HDMS‐β‐CD) with R‐,S‐solriamfetol, and heptakis(2,3‐O‐diacetyl‐6‐O‐sulfo)‐β‐CD (HDAS‐β‐CD) resulting S‐,R‐solriamfetol migration order. The sulfated‐γ‐CD system was chosen for method optimization applying orthogonal experimental design. The optimized method (45 mM Tris‐acetate buffer, pH 4.5, 4 mM S‐γ‐CD, 21°C, +19.5 kV) was capable for the baseline separation of solriamfetol and phenylalaninol enantiomers within 7 min. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of pharmaceutical preparation (Sunosi® 75 mg tablet), thus it may serve as a routine procedure for the laboratories of regulatory authorities as well as in Pharmacopoeias.