lorcaserin and suvorexant

Suvorexant (SVR), lorcaserin (LCR) and brivaracetam (BVR) have been recently approved for the treatment of insomnia, obesity and epilepsy, respectively. Despite their clinical uses, these drugs have some abuse potential and have been enlisted under the schedule IV (SVR, LVR) and schedule V (BVR) categories of the Controlled Substances Act. A sensitive UPLC-MS-MS assay was developed for simultaneously determining SVR, LCR and BVR in human plasma. The liquid-liquid extraction method, using tert-butyl methyl ether as an extracting solvent, was used for sample preparation. Chromatographic separation was performed by using the Acquity BEH C18 column, using 10 mM ammonium acetate/acetonitrile/formic acid (15/85/0.1%; v/v/v) as the mobile phase. For sample ionization, electrospray ionization was used in the positive-ion mode. The multiple-reaction monitoring mode was used for detecting and quantifying analytes by using separate precursor-to-product ion transitions. The assay was validated following the SWGTOX guidelines, and all validation results were within the acceptable limits. The calibration curves of the analytes in the plasma were found to be linear, and the coefficient of determination (R2) was ≥ 0.992 for all the three analytes. The limit of detection values for SVR, LCR and BVR were 0.08, 0.11 and 0.26 ng/mL, respectively, whereas the limit of quantification values were 0.16, 0.27 and 0.65 ng/mL, respectively. The assay developed in this study is suitable for the identification and quantification of SVR, LCR and BVR in the forensic laboratory.

Topics: Azepines; Benzazepines; Calibration; Chromatography, High Pressure Liquid; Humans; Limit of Detection; Liquid-Liquid Extraction; Prescription Drugs; Pyrrolidinones; Reference Standards; Reproducibility of Results; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry; Triazoles

This column is the first in a two-part series exploring lessons for psychiatric drug development that can be learned from the development of six central nervous system drugs with novel mechanisms of action over the past 25 years. Part 1 presents a brief overview of the neuroscience that supported the development of each drug, including the rationale for selecting a) the target, which in each case was a receptor for a specific neurotransmitter system, and b) the indication, which was based on an understanding of the role that target played in a specific neural circuit in the brain. The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.

Topics: Aprepitant; Azepines; Benzazepines; Central Nervous System Agents; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Indenes; Morpholines; Neurotransmitter Agents; Ondansetron; Quinoxalines; Triazoles; Varenicline