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超高效液相色谱-串联质谱-信息依赖性采集-增强子离子扫描法快速测定血液中五种常见有毒生物碱:中毒案例应用。

Rapid determination of five common toxic alkaloids in blood by UPLC-MRM-IDA-EPI: Application to poisoning case.

机构信息

Department of Forensic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.

Department of Forensic Medicine, Guizhou Medical University, Guiyang, Guizhou 550004, PR China.

出版信息

Leg Med (Tokyo). 2023 Jul;63:102267. doi: 10.1016/j.legalmed.2023.102267. Epub 2023 May 2.

DOI:10.1016/j.legalmed.2023.102267
PMID:37201269
Abstract

Toxic alkaloids are typically found in herbal medicines and have strong pharmacological effects and a broad therapeutic spectrum. On the other hand, toxic alkaloids exert toxicological activities in vivo; as such they have a narrow therapeutic window and can induce poisoning due to incorrect dose or misuse. In this view, there is an urgent need to develop a rapid and sensitive assay to detect these toxic alkaloids. This study developed a method for determining five common toxic alkaloids in blood, including brucine, strychnine, aconitine, mesaconitine, and hypaconitine using ultra-high liquid chromatography-tandem quadrupole/linear ion trap mass spectrometry (QTRAP UPLC-MS/MS). The analytes in this investigation were extracted with ether and detected using multiple reaction monitoring (MRM)-information-dependent acquisition (IDA)-enhanced product ion (EPI) scanning modes. SKF served as the internal standard (IS). The approach demonstrated excellent linearity, with a correlation coefficient (R) > 0.9964, and satisfactory sensitivity, with the limit of detection (LOD) of 0.31 ∼ 3.26 ng/mL and a limit of quantification (LOQ) of 1.13 ∼ 11.52 ng/mL. The extraction recovery (ER) was 78.8 ∼ 116.2%, the matrix effect (ME) was -12.3 ∼ 21.2%, and the method accuracy was 0.8 ∼ 12.8%. In addition, the intra-day precision and the inter-day precision (RSD) were 0.7% ∼ 7.4% and 0.4% ∼ 13.5%, respectively. The developed approach is sensitive and efficient, and offer significant application prospect in clinical monitoring and forensic detection of poisoning.

摘要

有毒生物碱通常存在于草药中,具有很强的药理作用和广泛的治疗谱。另一方面,有毒生物碱在体内发挥毒理学活性;因此,它们的治疗窗很窄,如果剂量不正确或使用不当,可能会导致中毒。在这种情况下,迫切需要开发一种快速灵敏的检测方法来检测这些有毒生物碱。本研究建立了一种采用超高效液相色谱-串联四极杆/线性离子阱质谱(QTRAP UPLC-MS/MS)测定血液中 5 种常见有毒生物碱的方法,包括马钱子碱、士的宁、乌头碱、次乌头碱和新乌头碱。本研究采用乙醚提取分析物,采用多反应监测(MRM)-信息依赖性采集(IDA)-增强子离子(EPI)扫描模式进行检测。SKF 作为内标(IS)。该方法具有良好的线性,相关系数(R)>0.9964,且灵敏度高,检测限(LOD)为 0.313.26ng/mL,定量限(LOQ)为 1.1311.52ng/mL。提取回收率(ER)为 78.8%116.2%,基质效应(ME)为-12.3%21.2%,方法准确度为 0.8%12.8%。此外,日内精密度和日间精密度(RSD)分别为 0.7%7.4%和 0.4%~13.5%。所建立的方法灵敏、高效,在临床中毒监测和法医毒物检测中具有广阔的应用前景。

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