Chiral analysis of ketamine enantiomers in human urine and hair: Application to authentic cases of ketamine use.

Ketamine, which possesses important anesthesia and antidepressant properties, has been used clinically in its racemate form. In the 1990s, the single enantiomer S-ketamine began to be used for clinical use. In 2019, an antidepressant S-ketamine hydrochloride nasal spray hit the market. Therefore, a method for chiral analysis of ketamine is particularly important, as this could reveal the types of drugs taken by individuals. An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the separation of chiral ketamine in human urine and hair in this study. Urine (50 μL) was diluted in 950 μL of methanol. Approximately 20 mg of hair was extracted in methanol by cryogenic grinding. The method was applied to authentic urine, blood, and 45 hair samples. Following the deceased's use of esketamine prior to death, only S-ketamine was found in the blood and urine, suggesting that ketamine does not undergo enantiomeric inversion in vivo. The ratio of R-ketamine to S-ketamine in 45 hair samples from ketamine abusers ranged from 0.809 to 1.43, indicating that the ketamine available on the illegal drug market was predominantly in its racemate form. Furthermore, a significant difference (P = 0.039) was observed in the enantiomeric ratio of ketamine between hair samples from ketamine abusers in China and Myanmar. The enantiomeric ratios found in ketamine sourced from various origins are potentially attributable to region variations and distinct synthetic routes. These findings provide a basis for analyzing ketamine enantiomers.