Division of Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
Division of Emergency Medicine, Iwate Medical University, Morioka, 020-8505, Japan.
J Food Drug Anal. 2019 Jul;27(3):786-792. doi: 10.1016/j.jfda.2019.02.001. Epub 2019 Feb 22.
Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 μL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x) was linear over the range of 1.56-200 μg/mL (r = 0.998), and the limit of detection and quantitation were 0.37 μg/mL and 1.56 μg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (-0.15-2.8% and 2.3-6.1%, respectively) and matrix effect at 3 concentrations (95.1-104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.
全球范围内，每年都会频繁发生药物中毒、误食毒物、自杀、他杀和接触有毒化合物等中毒事件。这就需要在临床急救环境中快速鉴定中毒患者中的有毒物质。此外，确定药物/毒物浓度无疑是制定毒理学治疗方案的必要条件。本研究旨在开发一种超快速药物筛选方法，用于临床中毒治疗。探针电喷雾电离（PESI）是一种大气离子化技术，几乎可以直接检测来自各种生物材料的化合物。我们将 PESI 技术应用于快速检测对乙酰氨基酚（APAP）。将血清样本用 10 mM 甲酸铵/乙醇（1:1 v/v）溶液稀释 100 倍，其中包含氘标记的内标物（APAP-d4）。仅使用 10 μL 稀释后的样品进行测量。配备 PESI 的串联质谱仪（MS/MS）用于定量分析 APAP，采用选择反应监测模式；测量时间仅为 18 秒。定量分析的离子跃迁设置为 152 > 110，定性分析的离子跃迁设置为 152 > 65，内标物（APAP-d4）的离子跃迁设置为 156 > 114。所有测量均在正模式下进行。校准曲线（1/x）在 1.56-200 μg/mL 范围内呈线性（r=0.998），检测限和定量限分别为 0.37 μg/mL 和 1.56 μg/mL。方法的准确度（偏差）和精密度（RSD%）均在可接受范围内（分别为-0.15-2.8%和 2.3-6.1%），3 个浓度（95.1-104%）的基质效应表明 PESI-MS/MS 仅受基质的轻微影响。在实际法医案例中，通过 PESI-MS/MS 定量测定的 APAP 值与通过液相色谱-MS/MS 方法测定的 APAP 值几乎相同。由于 PESI-MS/MS 是一种简单、可靠、快速的有毒物质测定方法，几乎不需要对血清进行预处理，因此非常适合临床急救环境中的中毒情况。未来，将开发一种同时快速测定多种有毒物质的方法。
