Mainero Rocca Lucia, L'Episcopo Nunziata, Gordiani Andrea, Staderini Alessandro
Chemical Agents Laboratory, Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, Italian Workers' Compensation Authority (INAIL), Monte Porzio Catone, Rome, Italy.
Rapid Commun Mass Spectrom. 2022 Apr 15;36(8):e9265. doi: 10.1002/rcm.9265.
An unconventional and innovative approach for the quantitative determination of 11 ototoxic and narcoleptic drugs in whole blood is described. The multiclass method allows the inclusion of the most widespread drugs on the market (antihistamines, antidepressants, antihypertensives, anxiolytics, opioids, Z-drugs) responsible for 10% of occupational accidents.
The developed procedure involved the use of the desorption electrospray ionization (DESI) interface for the direct analysis of dried blood spots (DBS). All the issues strictly connected to the chemical-physical characteristics of DBS and DESI (sample inhomogeneity, DBS support, DESI geometry and solvent) were carefully evaluated and innovative strategies were applied. Haematocrit was managed using a small and measured volume of blood (2 μL) with analysis of the entire DBS.
The proposed method was fully validated in terms of limits of detection, limits of quantitation (LOQs; between 60 pg/mm and 1.6 ng/mm ), linearity (one order of magnitude starting from LOQs) and inter- and intra-day precision (on three levels, with relative standard deviation values not exceeding 17%). Accuracy was calculated by comparison with an ultrahigh-performance liquid chromatography-tandem mass spectrometry method (suitable also as a confirmatory method).
Results showed a surprising sensitivity, demonstrating that this procedure could be suitable for applications in various fields, e.g. forensic analysis. Moreover, as a collateral benefit, it was discovered that the method is able to analyse very light traces left on plastic and glass surfaces by detached dried blood.
本文描述了一种用于定量测定全血中11种耳毒性和发作性睡病药物的非常规创新方法。该多类方法涵盖了市场上最常见的药物（抗组胺药、抗抑郁药、抗高血压药、抗焦虑药、阿片类药物、Z类药物），这些药物导致了10%的职业事故。
所开发的程序涉及使用解吸电喷雾电离（DESI）接口直接分析干血斑（DBS）。对所有与DBS和DESI的物理化学特性密切相关的问题（样品不均匀性、DBS载体、DESI几何形状和溶剂）进行了仔细评估，并应用了创新策略。通过使用少量且经过测量的血液体积（2μL）并分析整个DBS来控制血细胞比容。
所提出的方法在检测限、定量限（LOQ；60 pg/mm至1.6 ng/mm之间）、线性（从LOQ开始一个数量级）以及日内和日间精密度（在三个水平上，相对标准偏差值不超过17%）方面得到了充分验证。通过与超高效液相色谱 - 串联质谱法（也适用于确证方法）进行比较来计算准确度。
结果显示出惊人的灵敏度，表明该程序适用于各种领域的应用，例如法医分析。此外，作为附带好处，发现该方法能够分析由分离的干血留在塑料和玻璃表面上的非常微量的痕迹。
