Optimization of Exactive Orbitrap™ acquisition parameters for quantitative bioanalysis

Background: Orbitrap (TM) 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.