LC/MS Montreux

Symposium report of the “29th Montreux symposium on LC/MS” .

The 29th Montreux symposium on LC/MS was held from November 7-9 in the Montreux Music & Convention Centre (2M2C) in Montreux, Switzerland. Participants and exhibitors from 36 countries (top 5 : Switzerland, UK, The Netherlands, US, France)  all over the world gathered in the beautiful surroundings of Montreux.

This program of this event differed from previous symposia by the introduction of parallel sessions in addition to the LC/MS technology and applications focus, which were introduced to strengthen the topic of Metabolomics and to initiate the new topic of Clinical Chemistry. The latter is foreseen as an important attractor for new participants as the LCMS technology is entering in this domain. The Metabolomics society has been supporting the parallel program on metabolomics and in the scientific program this was clearly reflected. The unfortunate coinciding of other clinical chemistry events in the same week or  just before the Montreux symposium influenced the potential participants but the program was very attractive and is a clear opening to strengthen this further.

The LC/MS technique has become mature which was illustrated by again a shift towards more applications (oral and posters) in the program compared to the novel technology developments. Nevertheless, still intriguing new concepts were presented by instrumental companies, universities and industrial groups. In this respect the vendors have been very active as several lunch seminars were organized in the course of the symposium by major companies (Thermo, Waters and Agilent).

The conference was preceded with the traditional two day courses on the basics of “Practical LCMS” and the “Advanced interpretation of CID mass spectra from LC/MS/MS”  by Henion and Voyksner and with a new full-day course on “Metabolomics meets clinical chemistry”. This set of courses provided newcomers the opportunity to build their expertise to a level which enabled them to get the best out of the symposium and the extensive exhibition. The clinical oriented course served as a first step in developing an attractive course for clinical chemists with a recognized level of accreditation. In this course it was discussed (i) what metabolomics can learn from in-born errors of metabolism, and vice versa, (ii) what the requirements and future perspectives of study design for finding new biomarkers for clinical decision support are,  (iii) what the analytical requirements for LC/MS in the clinical labs are, and (iv) examples of LC/MS in the clinical lab.

After the opening of the symposium by the chairman Jan van der Greef also on behalf of the co-chairman Thomas Hankemeier, the opening “Roland W. Frei” lecture, was given by Jan Smeitink. Jan Smeitink is recognized as one of the experts in the field of Mitochondrial Medicine.  The take home message of his lecture related to “Omics technologies and Bioenergetics; application to Human disease” was the importance of integration of different biochemical levels and the need to include functional biological measurements to obtain a deeper understanding of disease. Examples were given on inborn errors of metabolism using genome wide screening complemented by proteomics and metabolomics. Based on the new biological knowledge new interventions can be developed accordingly. This also served as an entry into the domain of clinical chemistry for the following clinical chemistry parallel session.

In the clinical chemistry session Fowler gave an excellent introduction into the history of inborn error of metabolism research and ending in discussing how a better understanding of metabolic networks will result in a better diagnosis and treatment of metabolic diseases. Gross and others howled how ‘untargeted’ metabolite profiling can be applied for screening for inborn errors, and how to asses consequences of gene mutations, and how to identify mechanisms of drug actions. Boos presented trends and new approaches in sample preparation for the clinical lab including dried blood spots and whole blood analysis. Several methods were discussed for the analysis of clinically relevant biomolecules,  and whether high resolution MS detectors can replace triple quad MS detectors for high throughput quantitative analysis. Rinaldo ended the clinical session with an exciting demonstration how to analyze large data sets of population screening.

The common ground of metabolite screening between metabolomics and clinical chemistry formed a bridge in technology exchange and development of interesting strategies. Stimulating discussions were hold after lectures, but also during the poster sessions and coffee breaks on how MS-based metabolomics and other omics can bring new insights into the clinical and drug research, and what the requirements for these are. Many possible new collaborations were initiated in this way.

The plenary lecture of Thomas Hankemeier kick started the metabolomics session co-organized with the metabolomics society. His overview on metabolomics technologies was focused towards the application in pharmaceutical industry and tackling the challenge of personalized medicine. Methodology developed for important compound classes was demonstrated including micro-fluidics sample pre-treatment as well as biomarker discovery using these platforms as for instance in the cardiovascular area for responder/non-responder detection. Combination of new tracer-based methods for getting insights into mechanistic aspects as well as high throughput technologies to make the technique wider acceptable emphasized the important developments going on.

In the metabolomics session Cox and Zamboni showed how metabolomics can determine the function of genes; Zamboni also demonstrated the large scale analysis of 10,000’s of samples using direct-infusion MS. Examples of successful biomarker discovery were shown and how a clinical test was developed for these. The session was ended by an excellent lecture by Kastenmueller demonstrating what knowledge can be obtained when metabolomics and genomics data are combined in large cohort studies.

A topic emerging from sports doping and veterinary drug screening was the indirect detection of treatment or illegal use of drugs applying biomarker profiling (metabolomics, proteomics). This field in sports doping was discussed in an excellent way by Diel related to recent cases and illustrating new strategies for the future related to epigenetics and the ability to detect illegal use by monitoring various biochemical pathways simultaneously. This technology applied in horse racing and calf breeding was highlighted by a presentation from INRA to, clearly a new evolving tool using metabolomics and advance classification procedures.

Identification of unknown LCMS components remains a challenging task and an excellent keynote lecture by Robert Mistrik summarized the challenges and the state of the art of identification via MS/MS technology and spectral-trees. Intelligent use of cross species similarities and the structural continuum of sub-structures in biochemical pathways add considerably to the better interpretation options. In particular the mass spectral cloud relational database concept was explained. The power of high resolution in the process was emphasized. Various presentations were illustrating new workflows and data support platforms.

The further development of low cost LCMS instruments which are portable and could eventually compete with the UV-detection price level were discussed by Henion in a keynote lecture and by Zenobi in a plenary lecture. Henion emphasized the novel sample pretreatment instruments based on automation of dry blood spot analysis reaching low detection limits and quite high throughput. A technology very attractive for the pharmaceutical applications. Zenobi emphasized the 2nd MS revolution on ambient  mass spectrometry and showed various impressive examples of breath analysis, drug dosage studies, diagnostic applications etc. Desorption ionization (DESI) and Direct Analysis in Real Time (DART) as well as Secondary Electrospray Ionization (SESI) and Extractive Electrospray Ionization (EESI) were explained in terms of limitations and potential. In  other presentations among others IR-laser desorption atmospheric pressure photoionization mass spectrometry(LAAPI) was demonstrate with high spatial resolution.

Most mass spectrometry developments were related to improvement of existing technology but again some new approaches were presented as using in funnel technology and orbitrap instrument combined with an intelligent design with multi-poles elements. Traditionally sample pretreatment and separation science methodology is a strong area in the symposium in which new improvements were presented sometimes by improving “old” column materials such as porous graphitic carbon columns are shown to be very suitable in complex plant screening as it allows MS-friendly mobile phases. Automation of sample preparation using on-line combination of sample preparation and LC/MS analysis, use of microfluidics for sample preparation or interfacing with the MS, as well as new approaches for better quantification using better MS instrumentation.

Developments on the chromatography aspect of LC/MS often related to UPLC combined with TOFMS, but also comprised among others nano-UPLC quadrupole TOF-MS, Super critical chromatography (SFC), core-shell columns, microdyalisis combined with nanoLC, SCX-HILIC-MS for cationic polar metabolites and HPAEC. On-line electrochemistry MS for exploring phase 1 and II metabolism was demonstrated to be attractive.

In sample pretreament developments dried blood spot analysis in an automated workflow were highlighted in various presentations

Many applications in pharmaceutical, environmental, nutrition biotechnology were demonstrated. Keywords to illustrate the diversity of applications fields covered by LC/MS presentations are : forensic, doping, forensic toxicology, drugs of abuse, allergens, disease biomarkers (diabetes type 2, cardiovascular, cancer, obesity, migraine); multi-residue screening, DMPK, therapeutic drug monitoring,  bioanalysis of drugs, multi-residue screening, pesticides, occupational health, explosives, recombinant quality control, diet evaluation, xenobiotics and  biosimilars .

The “Roland W. Frei” poster award was on behalf of the poster-award committee presented by Prof Jose Broekaert as chairman of the IAEAC and was granted to Robert-Jan Raterink from Leiden university for his poster on “3-Phase electro-extraction : a Fast (online) sample preparation method to bioanalysis”. In addition two poster awards sponsored by Springer were given one to the best poster in metabolomics to Rezza Maleki from Delft University of Technology for the poster “Quantitative analysis of intracellular metabolites using isotope dilution ion pair reversed phase liquid chromatography tandem mass spectrometry and one to the best poster realted to clinical chemistry to Masoumeh Karimpour for the poster “LC/MS to study metabolite profiles in distal and proximal regions of healthy lungs after wood smoke exposure”.

The seemingly never-ending new inventions and applications in the field of mass spectrometry and new promising areas of metabolomics and clinical chemistry makes us look forward to the next event in again in November in Montreux , Switzerland. In 2013 the US-version will be organized by Bob Voyksner with an emphasis on food and food allergens while , due to the coincidence of the biannual IMSC meeting in Switzerland late August/beginning of September 2014, the next European Montreux symposium is foreseen in 2015.

Jan van der Greef and Thomas Hankemeier

Chairpersons of the Montreux LC/MS symposium

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