Liquid chromatography coupled to quadrupole‐based tandem mass spectrometry (QqQ) is termed the “gold standard” for bioanalytical applications because of its unpreceded selectivity, sensitivity, and the ruggedness of the technology. More recently, however, high‐resolution mass spectrometry (HRMS) has become increasingly popular for bioanalytical applications. Nonetheless, this technique is still viewed, either as a screening technology or as a research tool. Although HRMS is actively discussed during scientific conferences, it is yet to be widely utilised in routine laboratory settings and there remains a reluctance to use HRMS for quantitative measurements in regulated environments. This paper does not aim to comprehensively describe the potential of the latest HRMS technology, but rather, it focuses on what results can be obtained and outlines the author's experiences over a period of many years of the routine application of various forms of HRMS instrumentation. Fifteen years ago, some nine different QqQ methods were used in the author's laboratory to analyse a variety of different veterinary drug resides. Today, many more analytes are quantified by seven HRMS methods and just three QqQ methods remain in use for the analysis of a small set of compounds yet to be upgraded to HRMS analysis. This continual upgrading and migration of analytical methods were accompanied by regularly participating in laboratory proficiency tests (PTs). The PT reports (covering a range of analytes and analytical methods) were used to compare the accuracy of HRMS‐ versus QqQ‐based measurements. In the second part of this paper, the particular strengths and limitations of HRMS for both method development and routine measurements are critically discussed. This also includes some anecdotal experiences encountered when replacing QqQ assays with HRMS methods.

中文翻译：

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用于生物分析应用的高分辨率质谱：这是新的金标准吗？

液相色谱与基于四极杆串联质谱（QqQ）的质谱联用被称为生物分析应用的“金标准”，因为它具有前所未有的选择性，灵敏度和技术坚固性。但是，最近，高分辨率质谱（HRMS）在生物分析应用中变得越来越流行。尽管如此，该技术仍被视为筛查技术或研究工具。尽管在科学会议期间积极讨论了HRMS，但仍未在常规实验室环境中广泛使用HRMS，并且仍然不愿意在监管环境中使用HRMS进行定量测量。本文的目的不是全面描述最新HRMS技术的潜力，而是 它着重于可获得的结果，并概述了作者在各种形式的HRMS仪器的常规应用多年中的经验。十五年前，作者的实验室使用了大约九种不同的QqQ方法来分析各种不同的兽药残留。如今，通过7种HRMS方法对更多的分析物进行了定量，仅3种QqQ方法仍可用于分析一小部分尚未升级为HRMS分析的化合物。分析方法的不断升级和迁移伴随着定期参加实验室能力测试（PT）。PT报告（涵盖了一系列分析物和分析方法）用于比较基于HRMS和QqQ的测量的准确性。在本文的第二部分，严格讨论了HRMS在方法开发和常规测量方面的特殊优势和局限性。这还包括用HRMS方法代替QqQ分析时遇到的一些轶事。