Metabolic Profiler™ by Bruker Life Science Mass Spectrometry

Unique Metabolic Profiler™ Combines the Complementary Methods of Metabolite Quantitation and Structure Determination by NMR with Exact Mass Analysis by ESI-TOF Mass Spectrometry into an Integrated Metabonomics Solution

Chicago, Illinois, March 8, 2004  -  At the 2004 Pittsburgh Conference in Chicago, Bruker BioSpin Corporation and Bruker Daltonics Inc. (an operating subsidiary of Bruker BioSciences, NASDAQ: BRKR) today jointly introduce a unique and integrated system for metabolic profiling. This information-rich approach combines the strengths of both nuclear magnetic resonance (NMR) and time-of-flight (TOF) mass spectrometry (MS) into an integrated data acquisition, data evaluation and statistical model building solution for drug development.

The Metabolic Profiler system will be particularly applicable to toxicity and efficacy studies in pre-clinical and clinical development in the pharma and biotech industries. Moreover, this novel combined system is a powerful tool for clinical research in disease screening and patient stratification, with the potential to discover new small molecule diagnostic markers, or panels of metabolic markers.

Whereas genomics and proteomics have received a lot of attention in recent years, the realization that small molecules play an equally important role in the chemistry of biological systems has led to a growing field called metabonomics. The metabolic profile represents a snapshot of on-going biological processes, which has opened the door for the mining of metabolic profiles for biomarkers. The presence of a metabolite, panel of metabolites, or of a certain ratio of metabolites, can be an indication of a particular disease. This creates opportunities for early detection, ideally before the physical symptoms of a disease can be observed.

Metabolic analysis is also a key process in drug development in order to get early pre-clinical indications of efficacy and toxicity. It can be used to detect both the presence of drug metabolites, which may be surrogate markers of efficacy, and it can also detect the presence of certain compounds indicative of, for instance, liver toxicity. It is critical for drug development applications to detect toxicity in the earliest stages of a lead compound development, prior to expensive and time-consuming clinical trials.

The most information-rich techniques currently employed for metabolic profiling today are NMR and MS. On the one hand, NMR spectra of untreated samples represent an overview of all metabolites present in a body fluid. The complete NMR spectrum can be used as a fingerprint, and statistical techniques can be employed for screening purposes. On the other hand, LC/ESI-TOF can perform sensitive exact mass analysis of many metabolites. Following the identification of putative biomarkers, NMR can be used for determining their three-dimensional structure thereby maximizing the understanding of the biological processes.  Biomarker discovery companies can use this information-rich combined data to generate defensible intellectual property on metabolites.

Bruker BioSpin and Bruker Daltonics have jointly developed the Metabolic Profiler which combines for the first time in a fully integrated manner the strengths of NMR and ESI-TOF-MS.  By integrating an Avance™ Flow-NMR system that incorporates a unique 3 mm CryoFlowProbe™ (Bruker BioSpin) and the new high-performance microTOF™ ESI-TOF mass spectrometer with exact mass capabilities typically better than 3 ppm and a novel Sigma-Fit™ isotope pattern verification for automated molecular formula determination (Bruker Daltonics), the Metabolic Profiler represents a comprehensive systems solution for metabolic research and drug development. 

Along with the integrated hardware, the Metabolic Profiler provides easy to use software for system control and integrated data evaluation tools from statistics to structure elucidation.  NMR and MS spectral databases of reference compounds from all types of bio-fluids can be integrated to allow automatic verification of the presence of specified metabolites. Combining NMR and TOF-MS data in an advanced statistical analysis, visualization and model building information solution offers a new level of selectivity and specificity in metabolic profiling.

Metabolite tools

MetaboliteTools™ is a brand new software application for automated and interactive identification of drug metabolites using LC/MS.