Mephedrone: a single-dose administration study to determine human pharmacokinetics after nasal insufflation and to detect mephedrone and its metabolit

甲氧麻黄酮是英国使用最广泛的新型精神活性物质（“合法兴奋剂”）。它是一种合成卡西酮，2010年在英国被列为B类药物。尽管它很受欢迎，但关于甲氧麻黄酮药代动力学的人体数据很少。大多数可用的数据来自动物模型和因急性甲氧麻黄酮中毒而到医院就诊的个体的生物样本分析。我们计划进行一项人体给药研究，包括由健康男性志愿者鼻腔注入100毫克纯甲氧麻黄酮。将在特定时间点收集常规样本（血液、尿液、头发）以及替代生物基质（口服液、呼吸、干血斑、头汗、指印沉积物），并分析甲氧麻黄酮及其代谢物。替代的生物基质值得关注，因为它们不像血液/尿液那样需要严格的储存，而且更容易在药物治疗中心和路边药物测试等非专业环境中收集。将开发和验证样品制备和提取方法。LC - MS/MS将用于定量目标分析物的存在。只有一项人类志愿者研究（Papaseit等人）涉及口服甲氧麻黄酮。本研究有几个局限性：甲氧麻黄酮是从警方缉获的药物中获得的，样品纯度未进行评估；仅采集血样和尿样，未检测甲氧麻黄酮代谢物；甲氧麻黄酮是口服给药，而不是鼻腔注射。该项目将使我们的工业案例合作伙伴Alere毒理学受益，因为它将使他们能够将有效的分析纳入他们的业务。同时，该研究将更好地为医生治疗甲氧麻黄酮相关问题提供信息，也将在证据分析中具有价值。潜在的应用包括在押/监狱人员的测试、与犯罪有关的测试以及工作场所/路边的药物测试。

Mephedrone is the most widely used new psychoactive substance ("legal high") in the UK. It is a synthetic cathinone that was classified in the UK as a Class B drug in 2010.Despite its popularity there is very little human data on the pharmacokinetics of mephedrone. Most of the available data comes from animal models and biological sample analysis from individuals presenting to hospital with acute mephedrone toxicity. We plan to conduct a human administration study involving nasal insufflation of 100 mg of pure mephedrone by healthy male volunteers. Conventional samples (blood, urine, hair) as well as alternative biological matrices (oral fluid, breath, dried blood spots, head sweat, fingermark deposit) will be collected at specific time points and analysed for mephedrone and its metabolites. The alternative biological matrices are of interest as they require less stringent storage than blood/urine and can be easier to collect in non-specialist settings like drug treatment centres and in roadside drug testing. Sample preparation and extraction methods will be developed and validated. LC MS/MS will be used to quantify the presence of target analytes.There has only been one human volunteer study (Papaseit et al.) involving oral mephedrone administration. This study has several limitations: mephedrone was obtained from police seizures and sample purity was not assessed; only blood and urine samples were collected and mephedrone metabolites were not determined; and mephedrone was given orally rather than by nasal insufflation.The project will benefit our Industrial CASE Partner, Alere Toxicology, as it will enable them to incorporate validated assays into their business. At the same time, the study will better inform doctors in treating patients with mephedrone related problems and will also be of value in evidential analysis. Potential applications include testing of those in custody/prisons, testing related to crime and in workplace/roadside drug testing.