The Criminal Investigation Department of Beijing Public Security Bureau, Key Laboratory of Forensic Toxicology, Ministry of Public Security, 1st Longgang Road, Haidian District, Beijing 100085, China.
National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, China.
J Anal Toxicol. 2022 Apr 21;46(4):408-420. doi: 10.1093/jat/bkab034.
In 2020, 5F-MDMB-PICA (5F-MDMB-2201) was one of the most common synthetic cannabinoids (SCs) identified in drugs seized by the Beijing Drug Control Agency, and it was categorized as Schedule II by the United Nations Office on Drugs and Crime in March 2020. It is difficult to detect 5F-MDMB-PICA in biological matrices due to its fast metabolic rate in vivo. In this work, 5F-MDMB-PICA metabolic profiles were investigated by liquid chromatography--quadrupole exactive high field orbitrap mass spectrometer (LC-Q Exactive HF MS), with accurate mass measurements in human urine, serum and pubic hair. To obtain intact metabolites, solid-phase extraction for urine and serum and direct ultrasonic extraction for pubic hair were applied to clean the samples without enzymatic hydrolysis. The differences in 5F-MDMB-PICA metabolism in the three different matrices were compared for the first time to determine the best detection biomarkers for monitoring 5F-MDMB-PICA misuse. Urine samples were determined to be the preferred biological material for identifying 5F-MDMB-PICA abuse. Forty-seven intact metabolites were detected in human urine, the ester hydrolyzed with glucuronidated metabolite in urine samples can be used as the primary biomarker to identify drug misuse. Fifteen metabolites were found in serum samples. Ester hydrolysis was considered to be the major metabolic pathway, and a large number of metabolites were involved with it. Zero metabolites apart from the parent drug were detected in pubic hair samples. Twenty-eight new metabolites and their metabolic pathways were characterized and tentatively identified by LC-QE-HF-MS, and a new potential biomarker (M5 ester hydrolysis + propionic acid) was also identified.
2020 年，5F-MDMB-PICA（5F-MDMB-2201）是北京市药品监督管理局缴获的毒品中最常见的合成大麻素（SCs）之一，2020 年 3 月被联合国毒品和犯罪问题办公室列为附表二。由于其在体内的代谢速度很快，因此在生物基质中很难检测到 5F-MDMB-PICA。在这项工作中，采用液相色谱-四级杆精确质量高速轨道阱质谱（LC-Q Exactive HF MS）研究了 5F-MDMB-PICA 的代谢谱，在人尿、血清和阴毛中进行了准确质量测量。为了获得完整的代谢物，应用固相萃取法和直接超声提取法提取尿和血清中的样品，而无需进行酶解。首次比较了三种不同基质中 5F-MDMB-PICA 代谢的差异，以确定监测 5F-MDMB-PICA 滥用的最佳检测生物标志物。尿液样品被确定为识别 5F-MDMB-PICA 滥用的首选生物材料。在人尿中检测到 47 种完整的代谢物，尿中葡萄糖醛酸化代谢物的酯水解产物可用作识别药物滥用的主要生物标志物。在血清样品中发现了 15 种代谢物。酯水解被认为是主要的代谢途径，涉及大量的代谢物。在阴毛样品中除母体药物外未检测到其他代谢物。通过 LC-QE-HF-MS 对 28 种新代谢物及其代谢途径进行了表征和初步鉴定，并鉴定出一种新的潜在生物标志物（M5 酯水解+丙酸）。
