Metabonomics Subject

The NMR methods have been used in clinical medicine for many years, and metabonomic evaluation of human samples has been conducted for at least the past 10 years (28). Classical examples include the application of NMR to the evaluation of inborn errors of metabolism (29). More recent work has applied metabonomics to the evaluation of the clinical severity of coronary artery disease and to establish a relationship between serum metabolic profiles and hypertension (30,31). Because metabonomics is highly sensitive to environmental or dietary influences (discussed under toxicological applications), concern has been raised that the natural variation in the human population would preclude the application of metabonomics to clinical problems. However, such concerns have been dealt with directly, and recently, Lenz et al. (32) demonstrated that urine and plasma could be collected from human subjects and used successfully for metabonomic analyses. Furthermore, in addition to the disease states described above, metabonomics has been shown to a potentially useful tool for describing alterations associated with dietary and nutritional practices (33). 

In addition to characterization of disease states, NMR-based metabonomic analysis offers an efficient means to monitor the response of patients to drug therapy or other therapeutic interventions. For example, in a study of patients with end-stage renal failure, the response of patients to hemodialysis was monitored. Plasma samples were obtained from healthy subjects and from patients with renal failure immediately preceding and following hemodialysis. Samples were analyzed by NMR spectroscopy and mapped with pattern-recognition methods. Samples obtained from the majority of patients following hemodialysis were observed to map more closely to the cluster of samples obtained from healthy subjects than those samples obtained prior to dialysis therapy, with the exception of one patient who responded badly to the therapy and mapped separately to all other samples [13]. Thus, this methodology can be used to select appropriate therapies for patients. 

In the last decade, the held of metabonomics or metabolomics has experienced tremendous growth and has been the subject of numerous reviews in the literature [9-12], However, metabolite or metabolic profiling of low-molecular-weight... 

In another research article, Wang et al. [20] successfully applied LC-MS metabonomic techniques to the metabolite profiling of plasma phospholipids in type 2 diabetes mellitus (DM2) patients. Diabetes mellitus is associated with a metabolic disorder of lipid or fatty acid in phospholipids. The authors were not only able to differentiate between the samples from the DM2 patients and the healthy subjects but also identified a number of phospholipid molecular species that could be used as potential biomarkers for a differentiation of DM2 patients from the healthy individuals and perhaps even an early detection of DM2. 

Unlike other omics techniques, it is clear that metabonomics is very much an emerging field and new lessons on how to conduct a proper metabonomics study are learned each day. A very positive development is that in an effort to standardize the reporting standards for metabonomics studies, a first draft of a minimum requirement for the description of the biological materials and/or processes examined in a metabolomic study involving mammalian subjects was published in 2007 [89],... 

Designing a successful metabonomics experiment is truly a multidisciplinary exercise, and one must consider details of the in-life portion, sample collection, sample preparation, analytical data generation, data processing, analysis, and interpretation. The in-life portion involves study subjects selection, acclimatization, dosing or treatment, and sample collection and has been discussed in detail elsewhere (Robertson et al., 2002). The following sections will focus on the remaining steps in this process as it pertains to LC—MS. 

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