Department of Chemistry, National Chung Hsing University, 145 Xingda Rd., Taichung, 402, Taiwan.
Department of Chemistry, National Chung Hsing University, 145 Xingda Rd., Taichung, 402, Taiwan.
Anal Chim Acta. 2024 Nov 15;1329:343224. doi: 10.1016/j.aca.2024.343224. Epub 2024 Sep 11.
Drug abuse can result in both physical and mental health issues for individuals, and can also contribute to broader societal problems. The number of drug abuse cases rose to 296 million in 2021. The sample pretreatment methods commonly employed typically require longer processing times and occasionally necessitate derivatization. Furthermore, with the increase in sample sizes, traditional chromatography-mass spectrometry methods for analyzing abused drugs were no longer sufficient to handle such numerous samples. In this study, immuno-MALDI-MS chip were fabricated for specific enrichment of illicit drugs, integrating with the rapid and accurate capabilities of MALDI-MS for high-throughput analysis of drug abuse.
The immuno-MALDI-MS chip was successfully prepared by coating an aluminum chip with antibody-conjugated boronic acid-modified gold nanoparticles. Ketamine, a frequently abused illicit drug, served as the proof of concept for this study. The immuno-MALDI-MS chip was employed to selectively enrich ketamine in human urine samples, facilitating direct MALDI-MS analysis with the addition of α-CHCA matrix solution. The challenge of detecting abused drugs, exacerbated by interfering peaks in the low m/z region from salts and small molecules in human urine samples, was successfully overcome. The developed method exhibited a wide linear range of 10-5000 ng/mL with a limit of detection of 3.3 ng/mL for ketamine. Notably, the proposed method enabled high-throughput screening and accurate confirmation of ketamine concentrations in suspects' urine samples within few minutes, requiring a minimal sample volume of 1 μL. The obtained data were in complete agreement with the previous GC/MS analysis.
A straightforward, cost-effective and sensitive method for the selective enrichment and absolute quantification of abused drugs was developed using a homemade immuno-MALDI-MS chip integrated with MALDI-MS analysis. This method combines the advantages of immunoassay and mass spectrometry, offering both speed and accuracy. The reported method for the quantification of ketamine in human urine offers a practical approach and has the potential to analyze emerging new psychoactive substances in the future.
药物滥用会给个人带来身心健康问题，也会导致更广泛的社会问题。2021 年，药物滥用案例数量上升至 2.96 亿例。目前常用的样品预处理方法通常需要较长的处理时间，并且有时需要衍生化。此外，随着样品数量的增加，传统的用于分析滥用药物的色谱-质谱法已不足以处理如此多的样品。在这项研究中，我们制备了免疫-MALDI-MS 芯片，用于非法药物的特异性富集，并结合 MALDI-MS 的快速、准确特性，实现药物滥用的高通量分析。
通过在铝芯片上涂覆抗体偶联的硼酸修饰的金纳米粒子，成功制备了免疫-MALDI-MS 芯片。氯胺酮是一种经常被滥用的非法药物，作为本研究的概念验证。免疫-MALDI-MS 芯片用于选择性富集人尿样中的氯胺酮，通过加入α-CHCA 基质溶液直接进行 MALDI-MS 分析。该方法成功克服了人尿样中盐和小分子在低 m/z 区域产生的干扰峰对滥用药物检测的挑战。所开发的方法对氯胺酮的线性范围为 10-5000ng/mL，检测限为 3.3ng/mL。值得注意的是，该方法能够在几分钟内对嫌疑人尿样中的氯胺酮浓度进行高通量筛选和准确确证，所需样品体积仅为 1μL。获得的数据与之前的 GC/MS 分析完全一致。
本研究使用自制的免疫-MALDI-MS 芯片与 MALDI-MS 分析相结合，开发了一种用于滥用药物选择性富集和绝对定量的简单、经济高效且灵敏的方法。该方法结合了免疫测定和质谱的优势，兼具速度和准确性。本研究报道的人尿中氯胺酮的定量方法提供了一种实用的方法，并有潜力在未来分析新兴的新型精神活性物质。
