Bade Richard, Ghetia Maulik, White Jason M, Gerber Cobus
University of South Australia, UniSA: Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide 5000, South Australia, Australia.
Anal Methods. 2020 Jul 28;12(28):3637-3644. doi: 10.1039/d0ay00560f. Epub 2020 Jul 6.
Benzodiazepines are important prescription pharmaceuticals used to help in the treatment of anxiety and sleep disorders. However, they also have a strong potential for abuse. In this respect, illicit benzodiazepines, i.e. not prescribed in Australia and designer benzodiazepines, which are new compounds that are not legally prescribed in any jurisdiction, have emerged in the illicit Australian market in recent years. Designer benzodiazepines are a new class of new psychoactive substances (NPS) and are particularly dangerous due to limited toxicity information and propensity to be mistaken for conventional benzodiazepines, leading to severe side effects and potentially death. It is therefore important to assess the prevalence of the use of these compounds in the community. The current work presents a validated liquid chromatography-mass spectrometry method for 20 prescribed and designer benzodiazepines and metabolites: 7-amino nimetazepam, alpha-hydroxy alprazolam, alprazolam, clonazepam, delorazepam, deschloroetizolam, diazepam, diclazepam, etizolam, flubromazepam, flunitrazepam, lorazepam, lormetazepam, meclonazepam, midazolam, nimetazepam, nitrazepam, oxazepam, pyrazolam and temazepam. Quetiapine, a prescription sedative drug that has been diverted for non-medical use, was also validated. Limits of quantification were predominantly below 10 ng L, except for the ubiquitous oxazepam, quetiapine and temazepam, which were between 75-300 ng L. Stability, recovery and matrix effects were also examined. Finally, this method was applied to influent wastewater from South Australia, which showed the presence of many benzodiazepines including the NPS etizolam.
苯二氮䓬类药物是用于帮助治疗焦虑症和睡眠障碍的重要处方药。然而，它们也有很强的滥用潜力。在这方面，非法苯二氮䓬类药物，即在澳大利亚未开具处方的药物以及新型苯二氮䓬类药物（在任何司法管辖区均未合法开具处方的新化合物）近年来已出现在澳大利亚非法市场。新型苯二氮䓬类药物是一类新型精神活性物质（NPS），由于毒性信息有限且容易被误认为是传统苯二氮䓬类药物，会导致严重副作用甚至可能死亡，因此特别危险。因此，评估这些化合物在社区中的使用流行情况很重要。当前的研究提出了一种经过验证的液相色谱 - 质谱法，用于检测20种处方和新型苯二氮䓬类药物及其代谢物：7 - 氨基硝西泮、α - 羟基阿普唑仑、阿普唑仑、氯硝西泮、地洛西泮、去氯乙替唑仑、地西泮、双氯西泮、乙替唑仑、氟溴西泮、氟硝西泮、劳拉西泮、氯美扎酮、甲氯硝西泮、咪达唑仑、硝西泮、奥沙西泮、吡唑仑和替马西泮。喹硫平是一种已被用于非医疗用途的处方镇静药物，也经过了验证。除了普遍存在的奥沙西泮、喹硫平和替马西泮（其定量限在75 - 300 ng/L之间）外，其他物质的定量限主要低于10 ng/L。还研究了稳定性、回收率和基质效应。最后，该方法应用于南澳大利亚的进水废水，结果显示存在多种苯二氮䓬类药物，包括新型精神活性物质乙替唑仑。
