Simultaneous analysis by Quadrupole‐Orbitrap mass spectrometry and UHPLC‐MS/MS for the determination of sedative‐hypnotics and sleep inducers in adulterated products

Adulterated products are continuously detected in society and cause problems. In this study, we developed and validated a method for determining synthetic sedative‐hypnotics and sleep inducers, including barbital, benzodiazepam, zolpidem, and first‐generation antihistamines, in adulterated products using Quadrupole‐Orbitrap mass spectrometry and ultrahigh performance liquid chromatography with tandem mass spectrometry. In Quadrupole‐Orbitrap mass spectrometry analysis, target compounds were confirmed using a combination of retention time, mass tolerance, mass accuracy, and fragment ions. For quantification, several validation parameters were employed using ultrahigh performance liquid chromatography with tandem mass spectrometry. The limit of detection and limit of quantitation was 0.05–53 and 0.17–177 ng/mL, respectively. The correlation coefficient for linearity was more than 0.995. The intra‐ and interassay accuracies were 86–110 and 84–111%, respectively. Their precision values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean recoveries of target compounds in adulterated products ranged from 85 to 116%. The relative standard deviation of stability was less than 10.7% at 4°C for 48 h. The 144 adulterated products obtained over 3 years (2014–2016) from online and in‐person vendors were tested using established methods. After rapidly screening with Quadrupole‐Orbitrap mass spectrometry, the detected samples were quantified using ultrahigh performance liquid chromatography with tandem mass spectrometry. Two of them were adulterated with phenobarbital.