Chiral analysis of ketamine enantiomers in human urine and hair: Application to authentic cases of ketamine use.
Zhen Zhang, Yan Shi, Meiting Lin, Ping Xiang, Liying Zhou, Hejian Wu, Xin Wang
Journal of pharmaceutical and biomedical analysis August 15, 2025 DOI: 10.1016/j.jpba.2025.116824 via PubMed
Summary
AI-generated from the abstractA UHPLC-MS/MS method was developed to separate and measure the two mirror-image forms (enantiomers) of ketamine in human urine and hair. After a deceased person used esketamine before death, only S-ketamine appeared in blood and urine, indicating that ketamine does not switch between its enantiomeric forms in the body. In 45 hair samples from ketamine abusers, the ratio of R-ketamine to S-ketamine ranged from 0.809 to 1.43, showing that illegal-market ketamine is mostly racemic (equal parts both enantiomers). A significant difference in this ratio was found between samples from China and Myanmar, likely due to regional variations in synthetic routes.
Study at a glance
| Characteristics | Method development and observational analysis Peer reviewed |
|---|---|
| Sample size | 45 |
| Population | Ketamine abusers (hair samples) and one deceased individual (blood and urine) |
| Keywords | Drug testing Ketamine analysis Pharmaceutical analysis Chiral separation Enantiomer |
| Key finding | Ketamine does not undergo enantiomeric inversion in vivo, and illegal-market ketamine is predominantly racemic, with enantiomeric ratios varying by geographic origin. |
Abstract
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.