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合成卡西酮在血液中的稳定性。

Stability of Synthetic Cathinones in Blood.

作者信息

Glicksberg Lindsay, Kerrigan Sarah

机构信息

Department of Forensic Science, Sam Houston State University, Huntsville, TX, USA.

出版信息

J Anal Toxicol. 2017 Nov 1;41(9):711-719. doi: 10.1093/jat/bkx071.

Abstract

The synthetic cathinones are powerful psychostimulants that have been associated with impairment, intoxication and fatal overdose. Forensic laboratories must be able to identify these new drugs as part of antemortem and postmortem toxicology investigations. Preliminary reports have indicated that some of the synthetic cathinones are unstable in biological matrices. It is important to understand drug stability in biological evidence so that analytical findings can be interpreted appropriately. The objective of this study was to systematically evaluate the concentration, temperature and analyte-dependent stability of synthetic cathinones in preserved blood using liquid-chromatography/quadrupole-time of flight-mass spectrometry (LC/Q-TOF-MS). Cathinone stability was investigated at frozen, refrigerated, ambient and elevated temperature (-20°C, 4°C, 20°C and 32°C). Although no concentration dependent differences in stability were observed, cathinone stability was highly temperature and analyte-dependent. Substituents on the aromatic ring and nitrogen profoundly influenced stability. Tertiary amines (pyrrolidinyl analogs) were significantly more stable than their N-alkylated (secondary amine) counterparts. Furthermore, the methylenedioxy (MD) group also exerted a significant stabilizing effect, for both secondary and tertiary amines. The unsubstituted and ring-substituted secondary amines were the least stable, most notably 3-fluoromethcathinone (3-FMC). Under some conditions, significant losses were observed within hours of storage. Half-lives ranged from a little as 8 h (3-FMC) to 21 days (3,4-methylenedioxy-α-pyrrolidinobutiophenone, MDPBP) at elevated temperature (32°C). In contrast, half-lives ranged from 0.4 to >10 months when refrigerated and demonstrated even greater stability when frozen. Biological evidence may be subjected to a variety of environmental conditions prior to, and during transport to the laboratory. These findings highlight the need to consider the potential for both temperature and analyte-dependent differences. Due to the inherent instability of certain drugs within the class, quantitative drug findings in toxicological investigations must be interpreted with caution, and within the context of specimen storage and integrity.

摘要

合成卡西酮是强效精神兴奋剂,与机能损害、中毒及致命性过量服用有关。法医实验室必须能够识别这些新型毒品,作为生前和死后毒理学调查的一部分。初步报告表明,一些合成卡西酮在生物基质中不稳定。了解生物证据中的药物稳定性很重要,以便能够恰当地解释分析结果。本研究的目的是使用液相色谱/四极杆飞行时间质谱(LC/Q-TOF-MS)系统评估合成卡西酮在保存血液中的浓度、温度和分析物依赖性稳定性。在冷冻、冷藏、室温及高温(-20°C、4°C、20°C和32°C)条件下研究卡西酮的稳定性。虽然未观察到稳定性存在浓度依赖性差异,但卡西酮稳定性高度依赖温度和分析物。芳香环和氮上的取代基对稳定性有深远影响。叔胺(吡咯烷基类似物)比其N-烷基化(仲胺)对应物稳定得多。此外,亚甲二氧基(MD)基团对仲胺和叔胺都有显著的稳定作用。未取代和环取代的仲胺最不稳定,尤其是3-氟甲基卡西酮(3-FMC)。在某些条件下,储存数小时内就会观察到显著损失。在高温(32°C)下,半衰期从短至8小时(3-FMC)到21天(3,4-亚甲二氧基-α-吡咯烷基丁苯酮,MDPBP)不等。相比之下,冷藏时半衰期为0.4至>10个月,冷冻时稳定性更高。生物证据在运往实验室之前及运输过程中可能会受到各种环境条件影响。这些发现凸显了考虑温度和分析物依赖性差异可能性的必要性。由于该类中某些药物固有的不稳定性,毒理学调查中的定量药物结果必须谨慎解释,并结合样本储存和完整性情况。

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