Systems biology limiting factor

Another application of target metabolomics illustrative of the importance of isomeric/isobaric separation is in the field of pharmacokinetics. Pharmacokinetic studies focus on the absorption and distribution of drugs and their metabolites in biological systems. " A limiting factor in pharmacokinetic research is a requirement of high-throughput screening of isomeric metabolites. IM-MS is a rapid technique where isomeric separations occur within minutes. For example, IM-MS has been used to separate opiate metabolic isomers in less than 1 minute. ... 

Until recently it was assumed that with certain exceptions, such as ethanol and benzoic acid, the capacity of the enzyme system was not a rate-limiting factor in drug metabolism and the biological half-life of a drug could be represented by its plasma half-life and was independent of... 

This work demonstrated a number of new results and opportunities for ultrafast XAS 1) it is possible to work with highly dilute solutions in transmission mode without dramatic loss of signal-to-noise ratio. This is very promising as one can envision the study of samples, for which large concentrations are impossible to reach. Biologically relevant samples are usually investigated in solutions with up to 1 mmol/1 concentration, and we therefore can envision such studies on the ultrafast time scales in the near future. 2) It is possible to scan the time delay between the laser pump pulse and the x-ray probe pulse, and therefore follow the evolution of the system from the start. 3) It also demonstrated the operation of an optical-x-ray cross-correlator (Fig. 6.b). The time resolution is not a limiting factor and the experiments are feasible with sources of shorter x-ray pulses, provided the flux is not too low. 

Improvements in column technology, detector sensitivity and the development of new detection systems, have made possible the routine separation of picomole quantities of nucleic acid components in complex physiological matrices. The very sensitivity of most LC systems, however, which is invaluable in the analysis of biological samples, is often the limiting factor because of inadequate or ambiguous identification methods. Although tremendous advances have been made in the on-line combination of HPLC with spectroscopic techniques [e.g., mass spectrometry, Fourier transform infrared (FT/IR), nuclear magnetic resonance], their application has not become routine in most biochemical and biomedical laboratories. 

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