Quantification of suvorexant in urine using gas chromatography/mass spectrometry

Suvorexant (Belsomra^®) is a novel sedative hypnotic drug that is prescribed to promote sleep in patients with insomnia. It is the first of a new class of drugs classified as dual orexin receptor antagonists (DORAs). Sedative hypnotics with central nervous system depressant effects feature prominently in forensic toxicology investigations. For this reason, a new analytical method was developed to identify suvorexant in urine using liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS). Due to the absence of a commercially available isotopically labeled internal standard, estazolam-D5 was used due to its azepine, triazole and chlorinated functionality. The limit of detection and limit of quantitation was 10ng/mL and the linear range of the assay was 10-1000ng/mL. Accuracy and precision (%CV) were 98-101% and <11% at 30, 250 and 800ng/mL. Interferences from matrix and fifty common drugs were not present and processed samples were stable for 24h at room temperature. Suvorexant is a new drug of significant forensic interest due to its hypnotic and central nervous system depressant effects. The absence of commercially available metabolites and its chromatographic properties present some challenges in terms of identification. Nevertheless, a robust, reliable and sensitive assay was developed to identify suvorexant using GC/MS analysis.