HRMS using a Q-Exactive series mass spectrometer for regulated quantitative bioanalysis: how, when, and why to...

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Pharmaceutical Analysis

Background:

• High-resolution mass spectrometry (HRMS) is increasingly used in discovery workflows.
• Historically, HRMS sensitivity was insufficient for regulated bioanalysis, especially for low limit of quantification (LLOQ) assays.
• Previous comparisons showed HRMS data acceptable for regulated bioanalysis but lacking sensitivity versus triple quadrupole (QQQ) instruments.

Purpose of the Study:

• To evaluate the suitability of HRMS, specifically Q-Exactive series mass spectrometers, for regulated quantitative bioanalysis.
• To demonstrate how recent advances in HRMS have closed the sensitivity gap with QQQ instruments.
• To provide guidance on the implementation of HRMS in regulated quantitative bioanalysis.

Main Methods:

• Comparison of HRMS (Q-Exactive series) performance against QQQ instrumentation.
• Assessment of sensitivity, selectivity, and quantitative capabilities for bioanalytical assays.
• Evaluation of data quality for regulated environments.

Main Results:

• Recent HRMS instrumentation demonstrates comparable or superior sensitivity and selectivity to QQQ instruments.
• HRMS can achieve the required sensitivity for sub ng/ml LLOQ assays.
• HRMS provides data quality suitable for regulated quantitative bioanalysis.

Conclusions:

• HRMS, particularly the Q-Exactive series, is now a viable and advantageous option for regulated quantitative bioanalysis.
• The improved sensitivity and selectivity of modern HRMS systems overcome previous limitations.
• HRMS should be considered for implementation in late discovery and development bioanalytical assays.