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采用精确质量 LC-TOF-MS 对血清或血浆中的 67 种药物及代谢物进行快速筛选。

Rapid screening for 67 drugs and metabolites in serum or plasma by accurate-mass LC-TOF-MS.

机构信息

ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.

出版信息

J Anal Toxicol. 2012 Sep;36(7):477-86. doi: 10.1093/jat/bks061. Epub 2012 Jul 15.

DOI:10.1093/jat/bks061
PMID:22802572
Abstract

Sixty-seven drugs and metabolites were detected in serum or plasma using a fast (7.5 min) liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) method. This method was developed as a blood drug screen, with emphasis on the detection of common drugs of abuse and drugs used to manage chronic pain. Qualitative drug detection may identify a drug exposure, assure patient adherence with prescribed therapy and document abstinence from non-prescribed medications. Compound identification is based on chromatographic retention time, mass, isotope spacing and isotope abundance. Data analysis software (Agilent) generates a compound score based on how well these observed criteria matched theoretical and empirical values. The method was validated using fortified samples and 299 residual patient specimens (920 positive results). All results were confirmed by gas chromatography-MS or LC-tandem MS. The accuracy of positive results (samples meeting all qualitative criteria for retention time, mass and compound score) was >90% for drugs and/or metabolites, except for two benzodiazepines. There were 35 false positive results (seven compounds, 3.8%) that could be distinguished by retention time and/or absence of metabolites. The most frequent was 6-acetylmorphine in the absence of morphine. The LC-TOF-MS targeted screening method presented represents a sensitive and specific technology for drug screening of serum or plasma.

摘要

采用快速(7.5 分钟)液相色谱飞行时间质谱(LC-TOF-MS)法检测血清或血浆中的 67 种药物和代谢物。该方法被开发为血液药物筛查方法,重点检测常见的滥用药物和用于治疗慢性疼痛的药物。定性药物检测可识别药物暴露,确保患者遵守规定的治疗方案,并记录未经处方的药物的戒断情况。化合物鉴定基于色谱保留时间、质量、同位素间隔和同位素丰度。数据分析软件(Agilent)根据这些观察到的标准与理论和经验值的匹配程度生成化合物得分。该方法使用加标样品和 299 份剩余患者标本(920 份阳性结果)进行验证。所有结果均通过气相色谱-MS 或 LC-串联 MS 确认。阳性结果(满足保留时间、质量和化合物得分所有定性标准的样品)的准确性>90%,除了两种苯二氮䓬类药物。有 35 个假阳性结果(七种化合物,3.8%),可通过保留时间和/或无代谢物区分。最常见的是在没有吗啡的情况下出现 6-乙酰吗啡。所提出的 LC-TOF-MS 靶向筛选方法代表了血清或血浆药物筛选的一种敏感且特异性的技术。

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