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琥珀酰单胆碱作为琥珀酰胆碱给药标志物的适用性——致命性琥珀酰胆碱中毒与死后对照标本的比较分析。

Applicability of succinylmonocholine as a marker for succinylcholine administration--comparative analysis of samples from a fatal succinylcholine-intoxication versus postmortem control specimens.

机构信息

Institute of Forensic Medicine, University of Bonn, Stiftsplatz 12, 53111 Bonn, Germany.

出版信息

Forensic Sci Int. 2011 Apr 15;207(1-3):84-90. doi: 10.1016/j.forsciint.2010.09.007. Epub 2010 Oct 8.

DOI:10.1016/j.forsciint.2010.09.007
PMID:20934283
Abstract

Doubts concerning the applicability of succinylmonocholine (SMC) as a succinylcholine (SUX) marker have been issued. A comparative analysis of previously discussed tissues, i.e. brain, liver and kidney, was conducted to further elucidate this question by searching for diagnostically useful differences in analyte content in samples of SUX- versus non-SUX-associated fatalities. Furthermore, possible advantages of vitreous humor as a novel and promising target matrix for SUX analytics were assessed. Sample material of SUX-negative controls as well as the fatal SUX-intoxication was derived from frozen archive material and current autopsies. Samples were analyzed according to a modified protocol of a previously published and validated method employing ion-pairing solid-phase extraction and subsequent HPLC-MS/MS analysis. Standard addition was employed for quantification as well as an estimation of the analytical limits of the method. In all tested matrices, the method was proven to be sufficiently sensitive for the intended application. No indication of native SMC was found in controls of fresh tissues, nor in fresh or frozen vitreous humor. However, most of the samples were found to be positive for a previously reported interference with SMC's main ion transition, thereby falsely suggesting an SMC content of up to 139 ng/g, 126 ng/g, 165 ng/g and 93 ng/ml in brain, liver, kidney and vitreous humor, respectively. Contrasting the results for fresh sample material, SMC was detectable in some of the initially non-putrefied liver samples after long-term storage, as well as in massively decomposed SUX-negative control bodies. In this context, a microbial origin of the analyte may be assumed. All tissues as well as the vitreous humor of the fatal SUX-intoxication were negative for SUX and SMC. Just like serum, tissue and vitreous humor samples therefore do not allow a reliable diagnosis of a SUX-intoxication: in tissues this is due to the pronounced instability of both target analytes in these esterase-containing matrices, for vitreous humor an additional reason could be their insufficient incorporation into this medium.

摘要

人们对琥珀酰单胆碱(SMC)作为琥珀酰胆碱(SUX)标志物的适用性产生了怀疑。通过搜索 SUX 相关与非 SUX 相关致命性病例样本中分析物含量的诊断性差异,对先前讨论的组织(即脑、肝和肾)进行了比较分析,以进一步阐明这一问题。此外,还评估了作为 SUX 分析新的有前途的靶基质的玻璃体的可能优势。SUX 阴性对照的样本材料以及致命的 SUX 中毒的样本材料均来自冷冻档案材料和当前的尸检。根据先前发表并经过验证的方法的修改方案,使用离子对固相萃取和随后的 HPLC-MS/MS 分析对样本进行了分析。标准添加用于定量以及估计方法的分析限。在所有测试的基质中,该方法对于预期的应用均被证明是足够敏感的。在新鲜组织的对照物中,在新鲜或冷冻的玻璃体中,均未发现天然 SMC 的迹象。但是,大多数样本均被发现对先前报道的 SMC 主要离子跃迁的干扰呈阳性,从而错误地表明脑、肝、肾和玻璃体中的 SMC 含量分别高达 139ng/g、126ng/g、165ng/g 和 93ng/ml。与新鲜样本材料的结果相反,在长期储存后,一些最初未腐烂的肝样本以及大量分解的非 SUX 阴性对照尸体中可检测到 SMC。在这种情况下,可以假定分析物的微生物来源。所有组织以及致命的 SUX 中毒的玻璃体均对 SUX 和 SMC 呈阴性。与血清一样,组织和玻璃体样本因此不能可靠地诊断 SUX 中毒:在组织中,这是由于在这些含有酯酶的基质中目标分析物的稳定性明显降低,对于玻璃体,其原因可能是其在该介质中的掺入不足。

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