Etizolam is a benzodiazepine analogue that is approved for use in Japan, Italy and India but has recently appeared as a nonapproved product on the illicit drug market in Europe and North America. Etizolam was identified in a crystalline material seized at a Kentucky racetrack, raising concerns that this drug may have been used in racing. The aim of this study was to characterize the metabolism and excretion of etizolam in horses to generate information on its disposition and to incorporate the correct urinary and serum target analytes into anti‐doping screening procedures. Etizolam was administered both intravenous and orally at a dose of 0.1 mg/kg of body weight to three horses using a two‐way crossover design. Pre‐administration and post‐administration serum and urine samples were collected and experiments conducted to identify potential metabolites in these samples. Additionally, in vitro metabolism studies using horse liver S9 were undertaken to complement the in vivo metabolism studies. Numerous metabolites were id1entified in both serum and urine in additional to parent drug, with α‐hydroxy‐etizolam producing the most abundant analytical signal (in terms of signal intensity and duration of detection) of the identified metabolites in both matrices. Therefore, α‐hydroxy‐etizolam is considered to be the most appropriate analyte for detection for anti‐doping purposes. Analytical methods were developed and validated and then applied to post‐administration samples to generate concentrations of etizolam and its major metabolites in serum and urine, resulting in excretion profiles that can be used to guide approaches to detecting the use of the drug.

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苯二氮卓类似物依替唑仑在马体内的代谢和排泄

依替唑仑是一种苯二氮卓类似物，已获准在日本、意大利和印度使用，但最近在欧洲和北美的非法药物市场上作为未经批准的产品出现。在肯塔基州的一个赛马场查获的一种结晶材料中发现了依替唑仑，这引发了人们对该药物可能已用于比赛的担忧。本研究的目的是表征马中依替唑仑的代谢和排泄，以生成有关其处置的信息，并将正确的尿液和血清目标分析物纳入反兴奋剂筛查程序。采用双向交叉设计，将依替唑仑以 0.1 mg/kg 体重的剂量静脉内和口服给药至三匹马。收集给药前和给药后的血清和尿液样品，并进行实验以鉴定这些样品中的潜在代谢物。此外，还进行了使用马肝 S9 的体外代谢研究，以补充体内代谢研究。除了母体药物外，还在血清和尿液中鉴定了许多代谢物，α-羟基-依替唑仑对两种基质中鉴定的代谢物产生最丰富的分析信号（在信号强度和检测持续时间方面）。因此，α-羟基-依替唑仑被认为是用于反兴奋剂检测的最合适的分析物。开发并验证了分析方法，然后将其应用于给药后样品，以生成血清和尿液中依替唑仑及其主要代谢物的浓度，