High-resolution mass spectrometry for bioanalytical applications: Is this the new gold standard?

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.