Analysis of new designer drugs in post-mortem blood using high-resolution mass spectrometry.
Analysis of new designer drugs in post-mortem blood using high-resolution mass spectrometry.
复制标题
使用高分辨率质谱分析死后血液中的新设计药物。
DOI：
10.1093/jat/bku144
复制
发表时间：
2015
影响因子：
2.5
通讯作者：
S. Fu
中科院分区：
文献类型：
--
作者：
Daniel Pasin;Sergei Bidny;S. Fu
开发并验证了一种分析方法，用于检测和定量 37 种新设计药物，包括卡西酮、致幻苯乙胺和哌嗪。仅使用 100 µL 全血，使用乙腈进行盐析辅助液液萃取，以分离目标化合物，然后使用 Waters ACQUITY 超高效液相色谱仪与 Waters XEVO 四极杆飞行时间质谱仪进行色谱分离。 Mephedrone-d3 用作内标。梯度洗脱与 Waters ACQUITY HSS C18 色谱柱（2.1 × 150 mm，1.8 µm）结合使用。使用检测器在正电喷雾电离模式下通过 MS(E) 采集对样品进行分析。所有感兴趣的化合物在 15 分钟运行时间内得到解析，并根据分子离子、两个产物离子的精确质量和保留时间进行肯定鉴定。所有分析物校准曲线在 0.05-2 mg/L 范围内呈线性，大多数相关系数 (r(2)) 值 >0.98。检测限在0.007-0.07 mg/L范围内，定量限在0.05-0.1 mg/L范围内。所有分析物在提取后 48 小时内保持稳定，大多数分析物在冰箱中保存 1 周和 3 个冻融循环后在血液中保持稳定。浓度高达 10 mg/L 时未观察到残留，也没有常见治疗药物或内源性化合物的干扰。回收率范围为 71% 至 100%，并对空白、尸检和分解血液进行了基质效应评估。所有偏倚和%变异系数值分别在±15和≤15%的可接受值内（定量下限为±20和≤20%）。该方法应用于多个法医案件，其中受试者表现出设计药物中毒的行为特征，并且对一组药物的常规筛查呈阴性。
An analytical method was developed and validated for the purpose of detecting and quantifying 37 new designer drugs including cathinones, hallucinogenic phenethylamines and piperazines. Using only 100 µL whole blood, a salting-out-assisted liquid-liquid extraction with acetonitrile was performed to isolate target compounds followed by chromatographic separation using a Waters ACQUITY ultra performance liquid chromatograph coupled to a Waters XEVO quadrupole time-of-flight mass spectrometer. Mephedrone-d3 was used as an internal standard. A gradient elution was used in combination with a Waters ACQUITY HSS C18 column (2.1 × 150 mm, 1.8 µm). Samples were analyzed using the detector in positive electrospray ionization mode with MS(E) acquisition. All compounds of interest were resolved in a 15 min run time and positively identified based on accurate mass of the molecular ion, two product ions and retention time. All analyte calibration curves were linear over the range of 0.05-2 mg/L with most correlation coefficient (r(2)) values >0.98. The limits of detection were within the range of 0.007-0.07 mg/L and limits of quantification within 0.05-0.1 mg/L. All analytes were stable 48 h after extraction and most were stable in blood after 1 week stored in a refrigerator and 3 freeze-thaw cycles. No carryover was observed up to 10 mg/L and no interferences from common therapeutic drugs or endogenous compounds. Recoveries ranged from 71 to 100% and matrix effects were assessed for blank, post-mortem and decomposed blood. All bias and % coefficient of variation values were within the acceptable values of ±15 and ≤15%, respectively (±20 and ≤20% at lower limit of quantification). The method was applied to several forensic cases where the subject exhibited behavior characteristic of designer drug intoxication and where routine screening for a panel of drugs was negative.