Optimization of Exactive Orbitrap™ acquisition parameters for quantitative bioanalysis

Abstract

Background: Orbitrap™ mass spectrometry has made significant impacts in the qualitative field of mass spectrometry, and it can be a potentially powerful quantitative technique. Because the Orbitrap is a relatively new platform, our understanding of this technology is not as well-versed as other mass spectrometric techniques. Results: An investigation of the optimal acquisition parameters for quantitation was conducted for propranolol, reserpine, leucine enkephalin and neurotensin from mouse plasma samples. The lower limits of quantitation were demonstrated to be 1–3 nM while the quantitation linear dynamic range extends to four orders of magnitude. This level of performance is sufficient for most bioanalytical applications in drug discovery. Conclusion: Increasing the ion population in the Orbitrap improves detection and lowers the limit of quantitation, but the upper limit of quantitation can suffer. A better understanding of the operating parameters will help guide us toward better experimental designs and the best conditions for quantitation.