The George Washington University, 2100 Foxhall Road, NW, Washington, DC, 20007, USA.
Allegheny County Office of the Medical Examiner, 1520 Penn Ave., Pittsburgh, PA, 15222 USA.
J Chromatogr A. 2019 Jul 5;1596:183-193. doi: 10.1016/j.chroma.2019.03.011. Epub 2019 Mar 7.
Fentanyl and its derivatives are amongst the ever-growing list of emerging drugs which are impinging on current traditional analytical techniques employed in forensic laboratories. To avoid current regulations, fentanyl analogues are being illicitly synthesized by slight alterations of functional groups to the fentanyl skeleton leading to inaccurate identifications, thus posing the greatest challenge to laboratories. In this study, a novel analytical technique is presented in which gas chromatography (GC) is interfaced with both cold electron ionization mass spectrometric (cold EI MS) and vacuum ultraviolet (VUV) detection by the means of a flow splitter for the simultaneous qualitative and quantitative analysis of twenty-four fentanyl analogues, including seven sets of positional isomers. For most of the twenty-four analogues, enhanced molecular ions were obtained with at least 1% intensity relative to base peak. In addition to enhanced molecular ions, the GC-cold EI MS maintained fragmentation pathways observed by GCMS with classical electron ionization. For the most part, VUV detection resulted in unique VUV spectra for fentanyl analogues including positional isomers. The combination of these two complementary detectors in tandem with the high resolving power of the gas chromatograph, allows for higher confidence in analyte identification by the combination of retention times, cold EI mass spectra and VUV spectra. The preferred method for quantitation was based on VUV detection and offered excellent determination coefficients (R≥0.999) for most analytes over two orders of magnitude dynamic range, without the need for deuterated internal standards. For both run-to-run and day-to-day repeatability studies, at moderate solute concentrations, the correct fentanyl related compound was identified in almost every instance from a library containing all the fentanyl analogues plus hundreds of other analytes.
芬太尼及其衍生物是不断增加的新兴毒品之一，这些毒品正在影响法医实验室目前使用的传统分析技术。为了规避现行法规，芬太尼类似物通过对芬太尼骨架的官能团进行轻微改变而被非法合成，从而导致鉴定不准确，这对实验室构成了最大的挑战。在这项研究中，提出了一种新的分析技术，其中气相色谱（GC）通过分流器与冷电子电离质谱（冷 EI MS）和真空紫外线（VUV）检测相连接，用于同时定性和定量分析二十四种芬太尼类似物，包括七组位置异构体。对于二十四种类似物中的大多数，增强的分子离子的强度相对于基峰至少增加了 1%。除了增强的分子离子外，GC-冷 EI MS 还保持了 GC-MS 用经典电子电离观察到的碎裂途径。在大多数情况下，VUV 检测导致了包括位置异构体在内的芬太尼类似物的独特 VUV 光谱。这两种互补检测器的串联组合以及气相色谱仪的高分辨率，使得通过保留时间、冷 EI 质谱和 VUV 光谱的组合，对分析物的鉴定更有信心。定量的首选方法基于 VUV 检测，并为大多数分析物在两个数量级的动态范围内提供了极好的测定系数（R≥0.999），而无需氘化内标。对于运行间和日常重复性研究，在中等溶质浓度下，从包含所有芬太尼类似物和数百种其他分析物的库中，几乎在每种情况下都可以正确识别与芬太尼相关的化合物。
