Stability of Ketamine and Its Metabolites Norketamine and Dehydronorketamine in Human Biological Samples

Abstract

Ketamine is a NMDA receptor antagonist used since 1970 for the induction of anesthesia. It has a rapid onset and short duration of action, so it is a preferred agent for short-term surgical procedures. Ketamine possesses sedative and analgesic properties and maintains hemodynamic stability; it therefore is used in patients during the neuro-reanimation period (1). Ketamine produces posthypnotic emergence reactions, such as prolonged hallucination and delirium. The frequency of ketamine abuse is increasing (2), and fatal ketamine poisoning cases have been reported (3)(4). Ketamine is metabolized by the hepatic microsomal cytochrome P450 enzymes to two major metabolites, norketamine (NK) and dehydronorketamine (DHNK), which are further biotransformed to glucuronide conjugates and then excreted in the urine (5). The activities of these metabolites have not been well studied in humans, but in animals, it was reported that they possess an anesthetic effect and that they might be responsible for the emergent reactions to ketamine anesthesia (5). In view of the growing importance of ketamine, both as a therapeutic agent and more recently as a drug of abuse, we studied the stability of ketamine and its two major metabolites, NK and DHNK, in biological samples under various conditions to optimize the conditions for transport and storage of these biological samples. Little has been reported about the stability of ketamine and its metabolites in human blood samples. In a recent study, ketamine was found to be stable in plasma samples stored at −20 °C for up to 3 months (6). In this study, the stability of ketamine metabolites …