Baptiste Grund (1), Hugues Henry (2), Maciej Bromirski (3) and Bertrand Rochat (1*)
quantitative Mass Spectrometry Facility, University Hospital of Lausanne, CHUV, CH-1011 Lausanne, Switzerland, (2) Department des Laboratoires, CHUV; (4) Thermo Fisher Scientific, Bremen, Germany
As we see more and more demonstrations of the capability of high-resolution (HR)-MS instruments to perform sensitive and reliable quantification of a large variety of analytes in HR-full scan mode, we can consider that HRMS is the new gold standard MS analyzer for LCMS analyses (quantitative and qualitative). Examples showing the versatility and the performances of HRMS in HR-full scan will be presented: 1) routine quantification of drugs and endogenous metabolites in plasma extracts, 2) Qual/Quan analysis in a study of the fate of tamoxifen drug in humans and 3) targeted and untargeted metabolomics.
In the last few years, various authors have predicted that some or most triple-quadrupole mass spectrometry (MS) systems would be replaced by high-resolution (HRMS) instruments, particularly as we see more and more demonstrations of the capability of HRMS instruments to perform sensitive and reliable quantification of a large variety of analytes in HR-full scan mode. Indeed, it is now realistic to perform quantitative and qualitative (Quan/Qual) determinations with the same HRMS instrument.
Some authors have mentioned hurdles for this shift, however, such as of the cost of HRMS instruments, the inutility to record large HR full scan data, the lack of official guidelines, etc. Step by step, all of these hurdles are being overcome. In this oral presentation, we will discuss the use of new, affordable HRMS instruments (mainly Q-/Exactive-MS®) in quantitative and qualitative clinical analyses, demonstrating the sensitivity and selectivity of these instruments for this work.
First, examples of clinical quantification work mostly in HR-full scan will be presented. Determinations of drugs or endogenous metabolites such as testosterone, vitamine D and hepcidin peptide, will be shown and compared with results obtained with triple-quadrupole-MS performing ion transitions.
Secondly, we will present an example of Qual/Quan analysis in a study of the fate of an anti-cancer agent, tamoxifen, in humans. Whereas tamoxifen metabolism has been extensively studied over the last 20 years, sensitive and selective HR-full scan allowed us to identify, very rapidly, over 40 metabolites including new ones that had never been observed in vitro or in vivo. The LC-HRMS data allowed us to have the most complete picture of the fate of tamoxifen with up to 7th metabolite generation.
Finally, we will show metabolomics data for biomarker discovery in blood of patients with prostate cancer or Alzheimer disease (untargeted metabolomics) and for the follow-up of 100’s identified hydrophilic metabolites to study the oxidative stress in red blood cells stored in transfusion bags (targeted metabolomics). This omics type of analyses will show that recording phenotypes with 100’s of metabolites is realistic with HR-full scan acquisition, today. HRMS will open the door for the determination of metabolite phenotyping which gives personalized biological passports, one of the further stepd in clinical bioanalysis.
All these examples will underscore the reliability and versatility of HRMS instruments. Eventually, the presented data will show why high-resolution-MS is becoming the new gold standard MS analyzer in clinical labs. Indeed, the use of one MS technology for routine or research, quantitative or qualitative LC-MS analysis will simplify workflow, decrease overall costs and reduce the activation energy to start new research studies.