Laboratory of Toxicology, Federation of Toxicology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 10 rue Ambroise Paré, 75010 Paris, France.
Chemical and Biological Health Technologies Unit (UTCBS), CNRS UMR8258-U1022, University of Paris, 4 Avenue de l'Observatoire, 75006 Paris, France.
Molecules. 2023 Apr 14;28(8):3466. doi: 10.3390/molecules28083466.
In toxicology, screenings are routinely performed using chromatographic methods coupled to detection systems such as high-resolution mass spectrometry (HR/MS). The increase in specificity and sensitivity of HRMS is responsible for the development of methods for alternative samples such as Volumetric Adsorptive Micro-Sampling. Whole blood overloaded with 90 drugs was sampled with 20 µL Mitra to optimize the pre-analytical step as well as to determine the identification limits of drugs. Elution of chemicals was carried out in a solvent mixture through agitation and sonication. After dissolution, 10 μL was injected into the chromatographic system coupled to the Orbitrap HR/MS. Compounds were confirmed against the laboratory library. The clinical feasibility was assessed in fifteen poisoned patients using the simultaneous sampling of plasma, whole blood and Mitra. The optimized extraction procedure allowed us to confirm 87 compounds out of the 90 present in the spiked whole blood. Cannabis derivatives were not detected. For 82.2% of the investigated drugs, the identification limits were below 12.5 ng·mL, with the extraction yields ranging from 80.6 to 108.7%. Regarding the patients' analysis, 98% of the compounds in plasma were detected in Mitra compared to whole blood, with a satisfying concordance (R = 0.827). Our novel screening approach opens new insights into different toxicologic fields appropriate for pediatrics, forensics or to perform mass screening.
在毒理学中,通常使用色谱方法结合检测系统(如高分辨率质谱(HR/MS))进行筛选。HRMS 的特异性和灵敏度的提高是替代样品方法(如体积吸附微采样)发展的原因。用 20µL Mitra 对 90 种药物超负荷的全血进行采样,以优化分析前步骤,并确定药物的鉴定限。通过搅拌和超声处理,在溶剂混合物中洗脱化学物质。溶解后,将 10µL 注入与轨道阱 HR/MS 耦合的色谱系统。化合物通过与实验室库进行对比进行确认。在十五名中毒患者中评估了临床可行性,同时对血浆、全血和 Mitra 进行采样。优化的提取程序允许我们在加标的全血中确认 87 种化合物。未检测到大麻衍生化合物。对于 82.2%的研究药物,鉴定限低于 12.5ng·mL,提取产率范围为 80.6%至 108.7%。关于患者分析,与全血相比,Mitra 中检测到血浆中 98%的化合物,具有令人满意的一致性(R = 0.827)。我们新颖的筛选方法为儿科、法医学或进行大规模筛选提供了不同毒理学领域的新见解。