High-resolution MS in regulated bioanalysis: where are we now and where do we go from here?

While triple quadrupole MS remains the workhorse of bionanalytical laboratories, LC coupled with high-resolution MS (LC-HRMS) is making headway in drug discovery. LC-HRMS is well suited for quantitative bioanalysis with the inherent advantage of post-acquisition data mining, which is not possible wi...

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Veröffentlicht in:Bioanalysis 2013-05, Vol.5 (10), p.1277-1284
Hauptverfasser: Fung, Eliza N, Jemal, Mohammed, Aubry, Anne-Françoise
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Sprache:eng
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Zusammenfassung:While triple quadrupole MS remains the workhorse of bionanalytical laboratories, LC coupled with high-resolution MS (LC-HRMS) is making headway in drug discovery. LC-HRMS is well suited for quantitative bioanalysis with the inherent advantage of post-acquisition data mining, which is not possible with triple quadrupole systems operated in SRM mode. LC-HRMS can, thus, accomplish the core task of a bioanalytical laboratory--accurate determination of a targeted analyte--with the added bonus of being able to monitor other compounds of interest either at the time of sample analysis, or as an afterthought, after sample analysis, with no additional effort in sample preparation, chromatographic optimization or sample reinjection. Despite these advantages, LC-HRMS has not been broadly adopted in regulated bioanalytical laboratories. The slow progress in embracing the technology may be due, in part, to difficulties in replacing an entire fleet of triple quadrupole MS. Additional reasons are that data mining is of less benefit in development, especially late-stage, than in discovery and that the technical and regulatory challenges associated with the change of platform are perceived to be significant. In addition, the current platform of LC-HRMS introduced by instrument companies has not been tailored to the core responsibility of the bioanalytical community. In marketing current LC-HRMS systems, there is a tendency to combine the needs of the bioanalytical community with those of the drug metabolism community, despite their inherent differences. As a result, the current HRMS systems available lack some basic features desired for bioanalysis, but include features that are not important for bioanalysis making the systems unnecessarily complex and expensive. A simple, cost effective, ideal HRMS system for a bioanalytical laboratory would provide HRMS with high resolving power (the higher the better), no MS/MS capability, and with software suitable for quantitative analysis and appropriate for use in regulated laboratories. Under this scenario, one can foresee a future where part of the regulated bioanalytical work will be accomplished using LC-HRMS, reserving triple quadrupole-based LC-MS/MS for assays that require exquisite sensitivity.
ISSN:1757-6180
1757-6199
DOI:10.4155/bio.13.81