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Clinical Utility of an LC-MS/MS Seizure Panel for Common Drugs Involved in Drug-Induced Seizures

机译:LC-MS / MS癫痫发作小组对涉及药物诱发的癫痫发作的常见药物的临床实用性

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摘要

Approximately 6% of new-onset seizures are drug-related, but there is currently no reliable way to determine if a seizure is drug-induced. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool that allows simultaneous detection of numerous analytes of diverse chemical nature in patient samples. This allows a single analysis to incorporate many compounds relevant to a particular clinical presentation, such as suspected drug-induced seizures. We investigated whether results from a seizure panel using LC-MS/MS could affect patient care. We developed a semiquantitative LC-MS/MS assay to detect 12 chemically diverse drugs implicated in drug-related seizures. We collected leftover serum and plasma samples from patients who had seized, performed solid-phase extraction, and analyzed the samples using a hybrid triple quadrupole/linear ion trap mass spectrometer. After assembling a team of medical and toxicology experts, we developed and used a scoring system to determine whether the results of the seizure panel would have affected patient treatment in each case where a drug was detected. In an analysis of 157 samples from patients who seized, 17 (11%) were found to be positive for a drug on the seizure panel. The team of experts determined that the test results probably or definitely would have affected treatment in 7 (41%) of these cases. A test that detects the presence of drugs implicated in drug-induced seizures can help physicians determine if an unexplained seizure is drug-related and thus potentially better direct patient care. Additionally, LC-MS/MS is an effective tool for answering clinically driven questions.
机译:约有6%的新发癫痫发作与药物有关,但目前尚无可靠的方法来确定癫痫发作是否为药物诱发的。液相色谱-串联质谱(LC-MS / MS)是一种功能强大的工具,可以同时检测患者样品中多种化学性质的分析物。这样一来,单个分析即可纳入许多与特定临床表现相关的化合物,例如可疑药物诱发的癫痫发作。我们调查了使用LC-MS / MS的癫痫发作小组的结果是否会影响患者护理。我们开发了一种半定量LC-MS / MS分析法,以检测12种与药物相关的癫痫发作有关的化学上多样化的药物。我们收集了已检出患者的剩余血清和血浆样品,进行了固相萃取,并使用混合三重四极杆/线性离子阱质谱仪对样品进行了分析。在组建了一支医学和毒理学专家团队之后,我们开发并使用了评分系统来确定每次检测到药物时癫痫发作小组的结果是否会影响患者的治疗。在对来自癫痫发作患者的157个样品进行的分析中,癫痫发作面板上发现有17种药物(11%)呈阳性。专家小组确定测试结果可能或肯定会影响其中7例(41%)的治疗。一项检测药物与药物性癫痫发作有关的药物的检测可以帮助医生确定无法解释的癫痫发作是否与药物有关,从而有可能更好地指导患者护理。此外,LC-MS / MS是回答临床驱动问题的有效工具。

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    《Clinical Chemistry》 |2009年第1期|p.126-133|共8页
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    Julia C. Drees,1 Judy A. Stone,1,2 Kent R. Olson,3,4 Kathryn H. Meier,3,4 Alan M. Gelb,5 and Alan H. B. Wu1,2*1 Department of Laboratory Medicine, University of California-San Francisco, San Francisco, CA, 2 Clinical Laboratory, San Francisco General Hospital, San Francisco, CA, 3 Clinical Pharmacy, University of California-San Francisco, San Francisco, CA, 4 California Poison Control System, San Francisco Division, San Francisco, CA, 5 Emergency Medicine, University of California-San Francisco, San Francisco, CA.* Address correspondence to this author at: 2M Clinical Laboratory, 1001 Potrero Ave., San Francisco, CA 94110. Fax 415-206-3045, e-mail wualan@labmed2. ucsf.edu.Received May 21, 2008, accepted October 28, 2008.Previously published online at DOI: 10.1373/clinchem.2008.110858Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data, (b) drafting or revising the article for intellectual content, and (c) final approval of the published article.Authors' Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:Employment or Leadership: None declared.Consultant or Advisory Role: J.A. Stone, Applied Biosystems.Stock Ownership: None declared.Honoraria: None declared.Research Funding: This study received a collaborative instrument from Applied Biosystems.Expert Testimony: None declared.Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.Acknowledgments: The LC-MS/MS used in this study was provided by Applied Biosystems as part of a collaboration with the Regents of the University of California on behalf of its San Francisco Campus.,;

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