Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS/MS in Postmortem Casework
Analysis of Novel Synthetic Opioids U-47700, U-50488 and Furanyl Fentanyl by LC-MS/MS in Postmortem Casework
复制标题
DOI：
10.1093/jat/bkw086
复制
发表时间：
2016-11-16
影响因子：
2.5
通讯作者：
Logan, Barry K.
中科院分区：
文献类型：
--
作者：
Mohr, Amanda L. A.;Friscia, Melissa;Logan, Barry K.
继一系列合成大麻素和合成卡西酮衍生物之后，非法药物市场开始出现合成类阿片（包括芬太尼及其衍生物）和其他化学性质无关的类阿片激动剂（包括AH-7921和MT-45）的增加。在尸检案例中最常遇到的化合物是呋喃基芬太尼（N-（1-（2-苯乙基）-4-哌啶基）-N-苯基呋喃-2-甲酰胺，Fu-F）和U-47700（反式-3，4-二氯-N-（2-（二甲氨基）环己基）-N-甲基苯甲酰胺）。据报告，这两种药物都存在于海洛因供应中，并在娱乐性阿片类药物使用者中越来越受欢迎，但最初是由制药公司在20世纪70年代开发的，作为潜在的镇痛治疗剂。建立了血液样品中U-47700、U-50488和呋喃芬太尼的分析方法。共提交了20个尸检病例进行定量分析，这些病例最初被认为是海洛因或其他类阿片相关药物过量。对于呋喃基芬太尼，U-47770和U-50488的分析范围分别为1-500和1-100 ng/mL。所有化合物的检测限均为0.5 ng/mL。在该方法的范围内，U-47700是11例病例中唯一确认的药物，5例病例同时确认了U-47700和呋喃芬太尼，3例病例仅确认了呋喃芬太尼。U-47700的平均和中位血药浓度分别为253 ng/mL（+/-150）和247 ng/mL，范围为17-490 ng/mL。呋喃芬太尼的平均和中位血药浓度分别为26 ng/mL（+/-28）和12.9 ng/mL，范围为2.5-76 ng/mL。鉴于广泛的地理分布和死亡病例中的流行率增加，毒理学测试应扩大到包括对具有阿片类药物过量病史但不存在传统阿片类药物或数量不足以导致死亡的病例进行“设计阿片类药物”测试。
Following series of synthetic cannabinoid and synthetic cathinone derivatives, the illicit drug market has begun to see increased incidence of synthetic opioids including fentanyl and its derivatives, and other chemically unrelated opioid agonists including AH-7921 and MT-45. Among the most frequently encountered compounds in postmortem casework have been furanyl fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylfuran-2-carboxamide, Fu-F) and U-47700 (trans-3,4-dichloro-N-(2-(dimethylamino) cyclohexyl)-N-methylbenzamide). Both drugs have been reported to be present in the heroin supply and to be gaining popularity among recreational opioid users, but were initially developed by pharmaceutical companies in the 1970s as candidates for development as potential analgesic therapeutic agents. A method was developed and validated for the analysis of U-47700, U-50488 and furanyl fentanyl in blood specimens. A total of 20 postmortem cases, initially believed to be heroin or other opioid-related drug overdoses, were submitted for quantitative analysis. The analytical range for U-47770 and U-50488 was 1-500 and 1-100 ng/mL for furanyl fentanyl. The limit of detection was 0.5 ng/mL for all compounds. Within the scope of the method, U-47700 was the only confirmed drug in 11 of the cases, 5 cases were confirmed for both U-47700 and furanyl fentanyl, and 3 cases were confirmed only for furanyl fentanyl. The mean and median blood concentrations for U-47700 were 253 ng/mL (+/-150) and 247 ng/mL, respectively, range 17-490 ng/mL. The mean and median blood concentrations for furanyl fentanyl were 26 ng/mL (+/-28) and 12.9 ng/mL, respectively, range 2.5-76 ng/mL. Given the widespread geographical distribution and increase in prevalence in postmortem casework, toxicology testing should be expanded to include testing for "designer opioids" in cases with histories consistent with opioid overdose but with no traditional opioids present or insufficient quantities to account for death.