During the reproducibility validation for a time-of-flight (TOF) high-resolution mass spectrometry (HRMS) method set up to detect 61 drugs of abuse commonly encountered in the toxicology laboratory, it was noticed that, a number of compounds were not identified correctly during the between run analysis; the most difficult compounds to identify were norpropoxyphene, morphine, norbuprenorphine, nortriptyline, EDDP and tramadol. In subsequent patient comparison studies, screening a panel of 338 analytes, the TOF-HRMS method correctly identified 211 analytes over two runs, but did not identify 127. A total of 11 false positive results were identified by manual review of the data to be the result of confirmation ion signal-to-noise ratio(s) < 3, although one false positive that was difficult to resolve (i.e., identification of maprotiline as amitriptyline) was due to similar fragment ions and retention times. The TOF-HRMS method showed reasonable agreement with LC–MS/MS results, but there were a number of discrepant results. Additionally, the TOF-HRMS did detect five compounds missed by the LC–MS/MS methods. This extensive validation effort highlights the difficulty of analysis for certain compounds that are likely to require additional follow up prior to reporting a positive result, especially at low and high concentrations, regardless of the type of instrumentation involved.

在建立用于检测毒理学实验室中常见的61种滥用药物的飞行时间（TOF）高分辨率质谱（HRMS）方法的重现性验证期间，应注意的是，未鉴定出许多化合物在两次运行之间正确分析；最难鉴别的化合物是去甲丙氧芬，吗啡，去甲丁丙诺啡，去甲替林，EDDP和曲马多。在随后的患者比较研究中，通过筛选一组338种分析物，TOF-HRMS方法在两次运行中正确地鉴定了211种分析物，但没有鉴定出127种。通过人工检查数据，总共鉴定出11种假阳性结果为确认离子信噪比<3的结果，尽管一个假阳性很难解决（即，鉴定马普替林为阿米替林）是由于相似的碎片离子和保留时间。TOF-HRMS方法与LC-MS / MS结果显示出合理的一致性，但是有许多不一致的结果。此外，TOF-HRMS确实检测到LC-MS / MS方法遗漏的五种化合物。这种广泛的验证工作突显了某些化合物的分析难度，无论所涉及的仪器类型如何，在报告阳性结果之前，尤其是在低浓度和高浓度下，可能都需要进行其他后续跟踪。