Determination of the Presence of Daridorexant, a New Hypnotic, in Hair After a Single Exposure and Application to Repetitive Exposures

BACKGROUND: Daridorexant, a new hypnotic used to treat chronic insomnia in adults, has been marketed in France since March 2024. It is an orexin receptor antagonist that blocks orexin binding and promotes sleep without disrupting the natural sleep cycle. Daridorexant could be a good candidate for drug-facilitated crimes; however, to date, this has never been observed in such cases. This study aimed to identify daridorexant in hair. METHODS: A healthy male volunteer ingested a single 25-mg daridorexant tablet. Two locks of light-brown hair were collected 4 weeks later. After incubation at a basic pH and extraction using an appropriate solvent mixture, daridorexant was analyzed using liquid chromatography-tandem mass spectrometry (TSQ Altis Plus, Thermo Fisher Scientific). RESULTS: In the segment corresponding to the exposure time, daridorexant concentration was 0.029 pg/mg. The other segments were negative. To expand the detectability data for this molecule, a second study was conducted after repeated consumption of 25 mg daridorexant over 6 days. The results obtained are consistent with the findings of the first study, with a response at 0.8 pg/mg in the segment of interest. Furthermore, hair analysis of an assault victim revealed the presence of daridorexant at 35 pg/mg. In this case, the victim voluntarily consumed the prescribed daridorexant for 2 months after the assault to aid sleep. CONCLUSIONS: The authors report, for the first time, quantitative data on daridorexant detection in hair after single and repeated exposures. The test results are difficult to interpret because they represent the first data available in the literature. Nevertheless, the use of a sensitive analytical system, such as liquid chromatography-tandem mass spectrometry, seems necessary given the very low concentrations measured.