Isolation, Characterization, and Stability Assessment of Pure Enantiomers of Cathinone Derivatives via...

In addition to well-known traditional synthetic illicit drugs like cocaine, amphetamines, and heroin, an increasing number of new psychoactive substances (NPS) are appearing on the global drug market. Among them, cathinones represent a prominent class. These amphetamine-like compounds contain a stereogenic center, resulting in the possible presence of two enantiomers. Pure enantiomers of cathinone derivatives are not commonly available, and their production is cost-intensive. Thus, there is very little knowledge about the possible distinct effects of single enantiomers of cathinones. The objective of this study was to evaluate the stability of a set of eight cathinone derivatives, namely 3-methylethcathinone, 3-methylmethcathinone, 4-methylethcathinone, 4-methylmethcathinone, ethylone, 3,4-trimethylene-α-ethylaminovalerophenone, 3,4-tetramethylene-α-pyrrolidinovalerophenone, and 3,4-trimethylene-α-pyrrolidinobutiophenone, over a six-month period. Any racemization that may have occurred under different storage and solution conditions was monitored and compared. Pure enantiomeric fractions were collected on a multi-milligram scale using semi-preparative HPLC under isocratic normal-phase conditions. A Phenomenex Lux^® i-Cellulose-5, 5 μm 250 × 10 mm column containing cellulose tris(3,5-dichlorophenylcarbamate) served as the chiral selector. The tests showed that aqueous conditions, pH, temperature, chemical structure, sunlight, and oxygen influence compound stability. The long-term storage of cathinone derivative enantiomers was found to be optimal as solids under deep-freezing conditions or in a slightly acidified solvent where they are protected from air and light.