Pettersson Bergstrand Madeleine, Helander Anders, Hansson Therese, Beck Olof
Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Pharmacology, Karolinska University Laboratory, Stockholm, Sweden.
Drug Test Anal. 2017 Apr;9(4):640-645. doi: 10.1002/dta.2003. Epub 2016 Jul 1.
The emerging new psychoactive substances made available for recreational drug use have recently started to include designer benzodiazepines. As a consequence, the routine immunoassay drug testing for benzodiazepines may become less effective, due to an increased occurrence of 'false negative' and 'false positive' results. This work aimed to extend the knowledge of analytical cross-reactivity of 13 designer benzodiazepines in the CEDIA, EMIT II Plus, HEIA, and KIMS II immunoassays. Urine standards were prepared by spiking blank urine with clonazolam, deschloroetizolam, diclazepam, estazolam, etizolam, flubromazepam, flubromazolam, flutazolam, 3-hydroxyphenazepam, meclonazepam, nifoxipam, phenazepam, and pyrazolam. Authentic urine samples from intoxication cases identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were also investigated. For the spiked standard samples, the 13 designer benzodiazepines generally showed a high cross-reactivity in all assays. This was further confirmed when investigating their detectability in authentic urine samples from cases of drug intake. The test responses also indicated additional reactivity from metabolites. The lowest detectability in spiked samples was observed for flutazolam, which shows the most divergent chemical structure compared with the other benzodiazepines. Overall, the KIMS II and CEDIA immunoassays, which both include enzymatic hydrolysis of conjugated forms, showed the highest, and EMIT II Plus the lowest degree of reactivity, for spiked parent substances and authentic urine specimens. The results of this study demonstrated that designer benzodiazepines can be detected in standard urine immunoassay drug screening and this should be taken into consideration when performing confirmation analysis. Copyright © 2016 John Wiley & Sons, Ltd.
最近，可用于娱乐性药物使用的新型精神活性物质开始包括设计苯二氮䓬类药物。因此，由于“假阴性”和“假阳性”结果的发生率增加，苯二氮䓬类药物的常规免疫分析药物检测可能会变得不那么有效。这项工作旨在扩展对13种设计苯二氮䓬类药物在CEDIA、EMIT II Plus、HEIA和KIMS II免疫分析中的分析交叉反应性的认识。通过向空白尿液中添加氯硝西泮、去氯乙唑仑、地西泮、艾司唑仑、乙唑仑、氟溴西泮、氟溴唑仑、氟替唑仑、3-羟基芬那西泮、美克洛氮卓、尼福西泮、芬那西泮和吡唑仑来制备尿液标准品。还对通过液相色谱-串联质谱法（LC-MS/MS）鉴定的中毒病例的真实尿液样本进行了研究。对于加标标准样品，这13种设计苯二氮䓬类药物在所有分析中通常都表现出较高的交叉反应性。在研究它们在药物摄入病例的真实尿液样本中的可检测性时，这一点得到了进一步证实。测试反应还表明代谢物具有额外的反应性。在加标样品中，氟替唑仑的可检测性最低，与其他苯二氮䓬类药物相比，其化学结构差异最大。总体而言，对于加标母体物质和真实尿液标本，都包括结合形式酶促水解的KIMS II和CEDIA免疫分析显示出最高的反应性，而EMIT II Plus显示出最低的反应性。本研究结果表明，在标准尿液免疫分析药物筛查中可以检测到设计苯二氮䓬类药物，在进行确证分析时应考虑到这一点。版权所有© 2016约翰威立父子有限公司。
