[Research progress on chiral separation of amphetamines, ketamine, cathinones].

Enantiomers are ubiquitous in nature, and they are especially important in the field of pharmaceutical chemistry. Although the enantiomers of chiral drugs have identical chemical structures, they differ notably in their pharmacological, toxicological, pharmacokinetic, metabolic, and other biological activities. The same is true for amphetamines, ketamine, and cathinones, as the chiral separation of these three drugs is representative of drugs. Gas chromatography (GC), high performance liquid chromatography (HPLC), and capillary electrophoresis (CE) are widely used for the chiral separation of these three kinds of drugs. There are some similarities among the three methods for the chiral separation of amphetamines, ketamine, and cathinones: -trifluoroacetyl-L-prolinyl chloride and (+)-α-methoxy-α-trifluoromethylphenylacetic acid are the two typical chiral derivatization reagents used in GC. In HPLC, three kinds of chiral stationary phases are used: proteins, polysaccharides, and macrocyclic antibiotics. Cyclodextrin and its derivatives are most commonly used in CE. However, these three methods have inherent shortcomings. In the case of GC, impurities produced during chiral derivatization may interfere with the analysis, and high reaction temperatures affect the efficiency of chiral separation. HPLC has limited application scope and is expensive. In CE, there has no established process to determine the appropriate chiral selector. In recent years, research into application of the chiral separation of the above-mentioned three kinds of drugs has its own characteristics in forensic toxicology. The chiral separation of amphetamine drugs is mostly used to infer the prototype and synthesis route of drugs on the market. The chiral separation of ketamine involves a variety of biological samples. For cathinones, chiral separation methods emphasize their wide applicability. In this review, 66 reports published in professional local and overseas magazines during the past decade are collated. The characteristics of the enantiomers of amphetamines, ketamine, and cathinones as well as the mechanism of chiral recognition are briefly introduced. The commonness of the research and the application of chiral separation in forensic toxicology are reviewed. This paper proposes that the chiral separation of drugs can be further investigated from the following three aspects: 1) the use of computer technology to establish a molecular model for exploring the mechanism of chiral recognition; 2) developing new technologies for chiral separation and carrying out commercial research on the supercritical fluid method; 3) applying chiral separation to judicial practice, pharmaceutical research and development, and other practical fields.