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评估干血斑中巴比妥类药物的检测:使用不同提取方法的气相色谱-质谱联用、气相色谱-串联质谱和液相色谱-串联质谱的比较分析。

Evaluating the detection of barbiturates in dried blood spots: A comparative analysis using gas chromatography-mass spectrometry, gas chromatography-tandem mass spectrometry, and liquid chromatography-tandem mass spectrometry with different extraction methods.

机构信息

Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Science Platform, Key Laboratory of Forensic Sciences, Ministry of Justice, No.1347 Guangfuxi Road, Shanghai 200063, PR China; School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China.

Department of Forensic Toxicology, Academy of Forensic Science, Shanghai Key Laboratory of Forensic Medicine, Shanghai Forensic Science Platform, Key Laboratory of Forensic Sciences, Ministry of Justice, No.1347 Guangfuxi Road, Shanghai 200063, PR China.

出版信息

J Chromatogr A. 2024 Nov 22;1737:465434. doi: 10.1016/j.chroma.2024.465434. Epub 2024 Oct 18.

Abstract

Rapid and accurate characterization and quantitation of blood barbiturates and their combination drugs are very important for the clinical treatment of acute barbiturate poisoning. A comparison of dried blood spot (DBS) and traditional liquid-liquid extraction (LLE) in the pre-treatment stage, as well as a comparison of gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) as instrumental analysis methods, revealed differences in the analysis results of barbiturates and their combination drugs under different conditions. Based on these findings, we introduce a DBS-GC-MS/MS method. The developed and validated method showed good selectivity, sensitivity (LOD: 0.1 μg mL, LOQ: 0.2 μg mL), linearity (R>0.9992), trueness (<15 %, except for carbamazepine, at 29.4 %), and precision (<15 %). Recovery was also good for most target compounds, but significant matrix effects were evident. Compared with the LLE method, the DBS method has the benefits of easy sample collection, storage, and transport, as well as simple pre-treatment and reduced reagent and energy consumption. Compared to LC-MS/MS, GC-MS/MS requires no switching between positive and negative ion modes and uses the MRM detection mode, meaning that more information about the sample compounds can be obtained in less analysis time. Using actual sample analysis, we have demonstrated the advantages of the DBS-GC-MS/MS method for the qualitative and quantitative analysis of barbiturates and poisoning events due to combinations of these drugs. Comparison of the three instruments and the two treatment methods revealed their analysis characteristics. From the perspective of practical application, the broad practical value and advantages of DBS should be embraced in more applications, and future analytical laboratory development should continue to recognize GC-MS/MS as a useful supplement to LC-MS/MS.

摘要

快速准确地对血液中的巴比妥类药物及其复方制剂进行定性定量分析,对于急性巴比妥类药物中毒的临床治疗非常重要。比较了干血斑(DBS)和传统液液萃取(LLE)在预处理阶段的差异,以及气相色谱-质谱(GC-MS)、气相色谱-串联质谱(GC-MS/MS)和液相色谱-串联质谱(LC-MS/MS)作为仪器分析方法的差异,发现不同条件下巴比妥类药物及其复方制剂的分析结果存在差异。在此基础上,我们引入了 DBS-GC-MS/MS 方法。所建立和验证的方法显示出良好的选择性、灵敏度(LOD:0.1μg·mL-1,LOQ:0.2μg·mL-1)、线性(R>0.9992)、准确度(<15%,除了卡马西平在 29.4%时为 15%)和精密度(<15%)。大多数目标化合物的回收率也很好,但基质效应明显。与 LLE 方法相比,DBS 方法具有易于采集、储存和运输样本,预处理简单,减少试剂和能源消耗的优点。与 LC-MS/MS 相比,GC-MS/MS 无需在正负离子模式之间切换,并采用 MRM 检测模式,这意味着在更短的分析时间内可以获得更多关于样品化合物的信息。通过实际样品分析,我们证明了 DBS-GC-MS/MS 方法在巴比妥类药物定性定量分析以及这些药物联合中毒事件中的优势。三种仪器和两种处理方法的比较揭示了它们的分析特点。从实际应用的角度来看,应该在更多的应用中接受 DBS 的广泛实际价值和优势,未来分析实验室的发展应继续将 GC-MS/MS 视为 LC-MS/MS 的有用补充。

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