Ketamine chiral analysis in alternative and innovative biological samples

Abstract

Ketamine ((R,S-2-(2-chlorophenyl)-2-methylamino)cyclohexanone) is a phencyclidine derivative used in human and veterinary clinical practice since 1970. It is a dissociative anaesthetic agent that induces also analgesia by non-opioid mechanisms. Ketamine causes a state of "dissociative anaesthesia", for this reason is used as a recreational drug and has been included in the controlled substance schedules of most countries. As an anaesthetic drug, Ketamine is commercially available as a racemic mixture however, (R)-Ketamine and (S)-Ketamine have significantly different pharmacodynamic activities: the therapeutic potency of (S)-Ket is 2-4 times greater than the that of the (R)-enantiomer, as regards anaesthetic and analgesic effects. Moreover, the post-hypnotic stimulatory properties and agitated behaviour are associated with (R)-Ket. On the other hand, even if Ketamine hallucinogenic potency is still largely unclear, some authors claim that the (R)-enantiomer is the most potent one. It has also been reported that (R)- and (S)-Ket have significantly different pharmacokinetic profiles. Thus, it is evident the need to provide analytical methods able to discriminate and simultaneously quantify both Ketamine enantiomers in biological matrices for pharmacokinetic, toxicological and forensic purposes. The aim of this study is the development of an analytical method for Ketamine chiral analysis in alternative and innovative biological fluids and tissues, such as Dried Blood Spots (DBSs), saliva and hair. Different chromatographic setups were tested to obtain a good enantioseparation by liquid chromatography with fluorimetric detection (HPLC-F). The assays are currently under validation and seem to be promising for a successfull Ketamine enantiomeric resolution and determination, in order to be applied to real biological samples

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