Fleming Steven W, Cooley Justin C, Johnson Leonard, Frazee C Clinton, Domanski Kristina, Kleinschmidt Kurt, Garg Uttam
Gulfstream Diagnostics, 9301 N Central Expressway, Tower 2, Ste 335, Dallas, TX75231, USA.
Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals and Clinics , 2401 Gillham Rd., Kansas City, MO 64108, USA.
J Anal Toxicol. 2017 Apr 1;41(3):173-180. doi: 10.1093/jat/bkw131.
The illicit drug market has rapidly evolved from synthetic cannabinoids to cathinone derivatives and now a new emerging threat of synthetic opioids. These compounds were mostly developed by pharmaceutical companies during drug discovery. The new psychoactive substances are not routinely covered in drug screening and may go undetected. Recently fentanyl analogous, AH-7921, MT-45 and now U-47700 have been encountered in clinical and forensic casework. U-47700 is gaining popularity on drug user forms as a legal alternative to heroin. It is a µ-receptor agonist that is part of the trans-1-2-diamine opioid analgesic drug class developed by The Upjohn Company in an attempt to develop a non-addicting analgesic. A LC-MS-MS method was developed and validated to detect and quantify U-47700. Additional analysis was conducted with an LC-QToF to identify the presence of the parent drug and metabolites. A total of four cases have been evaluated by the LC-MS-MS methodology which has an analytical range of 1-1,250 ng/mL and limit of detection of 1 ng/mL. The concentration of U-47700 in urine specimens ranged from below the limit of quantification to 224 ng/mL. The ToF analysis detected the presence of suspected phase I demethylated metabolites that may assist future analysis of this compound. The prevalence of designer opioids in casework highlights the importance of analysis for new psychoactive substances. Traditional opiates/opioids were not detected in the presented cases, but the available case histories revealed an opioid toxidrome. These findings suggest that U-47700 drug may cause significant morbidity and mortality within the United States as an emerging drug threat.
非法药物市场已迅速从合成大麻素演变为卡西酮衍生物，如今又出现了合成阿片类药物这一新兴威胁。这些化合物大多是制药公司在药物研发过程中开发的。新型精神活性物质在药物筛查中通常未被涵盖，可能无法被检测到。最近，在临床和法医工作中发现了芬太尼类似物AH - 7921、MT - 45以及现在的U - 47700。U - 47700在吸毒者群体中越来越受欢迎，成为海洛因的合法替代品。它是一种μ受体激动剂，属于由Upjohn公司开发的反式 - 1,2 - 二胺类阿片类镇痛药，该公司试图开发一种无成瘾性的镇痛药。开发并验证了一种液相色谱 - 串联质谱法（LC - MS - MS）来检测和定量U - 47700。使用液相色谱 - 四极杆飞行时间质谱仪（LC - QToF）进行了额外分析，以确定母体药物和代谢物的存在。共有4例案件通过LC - MS - MS方法进行了评估，该方法的分析范围为1 - 1250 ng/mL，检测限为1 ng/mL。尿液样本中U - 47700的浓度范围从低于定量限到224 ng/mL。飞行时间质谱分析检测到了疑似I期去甲基代谢物的存在，这可能有助于对该化合物的进一步分析。法医工作中新型阿片类药物的流行凸显了对新型精神活性物质进行分析的重要性。在所呈现的案件中未检测到传统阿片类药物，但现有的病例记录显示存在阿片类中毒症状。这些发现表明，作为一种新出现的药物威胁，U - 47700药物可能在美国导致显著的发病率和死亡率。
