未经批准:使用非法制造的合成阿片类药物,特别是芬太尼及其类似物,在过去的十年里,美国呈指数级增长。由于临床实验室中药物检测方法的针对性和不断发展的关注合成阿片类药物清单,需要替代的分析方法。
UNASSIGNED:使用疾病控制和预防中心(CDC)生产的芬太尼类似物筛查(FAS)试剂盒,我们开发了液相色谱-高分辨率质谱(LC-HRMS)合成阿片光谱库和数据采集方法,使用产物离子光谱的信息依赖性采集。色谱保留时间,检测限和基体效应,在尿液和血清中,建立了FAS试剂盒中的合成阿片类药物(n=150)。2019年(n=856)和2021年(n=878)发送到临床毒理学实验室进行全面药物检测的所有尿液和血清标本均使用FASLC-HRMS库进行分析,以确定芬太尼类似物和其他合成阿片类药物的患病率,回顾性(2019年)和前瞻性(2021年)。
UNASSIGNED:每种阿片类药物的检测限(LOD)范围为1至10ng/mL(中位数,尿液中的2.5ng/mL)和0.25-2.5ng/mL(中位数,血清中0.5ng/mL)。基质效应范围从-79%到86%(中位数,-37%)用于尿液,在稀释和直接分析之后,和-80%至400%(中位数,0%)为血清,蛋白质沉淀后。从2019年到2021年,血清样品中芬太尼/芬太尼类似物的患病率略有增加,而尿液中的患病率保持不变。仅有2个样品被鉴定为含有芬太尼类似物而没有芬太尼或芬太尼代谢物的共存。对已建立的MS/MS光谱库的分析揭示了大多数芬太尼类似物的特征性片段模式,可用于未来类似物的结构阐明和药物鉴定。
UNASSIGNED:LC-HRMS方法能够检测送去进行全面药物检测的常规样品中的芬太尼类似物。该方法可以适应不断发展的阿片类药物流行的测试需求。
UNASSIGNED: The use of illicitly manufactured synthetic opioids, specifically fentanyl and its analogs, has escalated exponentially in the United States over the last decade. Due to the targeted nature of drug detection methods in clinical laboratories and the ever-evolving list of synthetic opioids of concern, alternative analytical approaches are needed.
UNASSIGNED: Using the fentanyl analog screening (FAS) kit produced by the Centers for Disease Control and Prevention (CDC), we developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) synthetic opioid spectral library and data acquisition method using information dependent acquisition of product ion spectra. Chromatographic retention times, limits of detection and matrix effects, in urine and serum, for the synthetic opioids in the FAS kit (n = 150) were established. All urine and serum specimens sent to a clinical toxicology laboratory for comprehensive drug testing in 2019 (n = 856) and 2021 (n = 878) were analyzed with the FAS LC-HRMS library to determine the prevalence of fentanyl analogs and other synthetic opioids, retrospectively (2019) and prospectively (2021).
UNASSIGNED: The limit of detection (LOD) of each opioid ranged from 1 to 10 ng/mL (median, 2.5 ng/mL) in urine and 0.25-2.5 ng/mL (median, 0.5 ng/mL) in serum. Matrix effects ranged from -79 % to 86 % (median, -37 %) for urine, following dilution and direct analysis, and -80 % to 400 % (median, 0 %) for serum, following protein precipitation. The prevalence of fentanyl/fentanyl analogs in serum samples increased slightly from 2019 to 2021 while it remained the same in urine. There were only 2 samples identified that contained a fentanyl analog without the co-occurrence of fentanyl or fentanyl metabolites. Analysis of the established MS/MS spectral library revealed characteristic fragmentation patterns in most fentanyl analogs, which can be used for structure elucidation and drug identification of future analogs.
UNASSIGNED: The LC-HRMS method was capable of detecting fentanyl analogs in routine samples sent for comprehensive drug testing. The method can be adapted to accommodate testing needs for the evolving opioid epidemic.