Quantitative performance of a quadrupole-orbitrap-MS in targeted LC–MS determinations of small molecules

• Quantitative LC–MS performance of a new and affordable Q-orbitrap HRMS has been tested with 18 compounds in HR-full scan or MS/MS acquisition.
• Sensitivity, dynamic range of calibration curves and mass accuracy were the main aspects studied.
• Exact same plasma extracts and similar LC systems and conditions have been used and tested on the HRMS and a recent QQQ-MS.
• Results show similar performances with both low and high resolution MS platforms.
• Versatility and quantitative performance of HRMS in LC–MS analyses should reinforce HRMS instruments as key players in most laboratories.

High-resolution mass spectrometry (HRMS) has been associated with qualitative and research analysis and QQQ-MS with quantitative and routine analysis. This view is now challenged and for this reason, we have evaluated the quantitative LC–MS performance of a new high-resolution mass spectrometer (HRMS), a Q-orbitrap-MS, and compared the results obtained with a recent triple-quadrupole MS (QQQ-MS). High-resolution full-scan (HR-FS) and MS/MS acquisitions have been tested with real plasma extracts or pure standards. Limits of detection, dynamic range, mass accuracy and false positive or false negative detections have been determined or investigated with protease inhibitors, tyrosine kinase inhibitors, steroids and metanephrines. Our quantitative results show that today’s available HRMS are reliable and sensitive quantitative instruments and comparable to QQQ-MS quantitative performance. Taking into account their versatility, user-friendliness and robustness, we believe that HRMS should be seen more and more as key instruments in quantitative LC–MS analyses. In this scenario, most targeted LC-HRMS analyses should be performed by HR-FS recording virtually “all” ions. In addition to absolute quantifications, HR-FS will allow the relative quantifications of hundreds of metabolites in plasma revealing individual’s metabolome and exposome. This phenotyping of known metabolites should promote HRMS in clinical environment. A few other LC-HRMS analyses should be performed in single-ion-monitoring or MS/MS mode when increased sensitivity and/or detection selectivity will be necessary.

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