Poster Presentation 23rd Annual Lorne Proteomics Symposium 2018

Robust reproducible LC/MS based metabolomic profiling of large cohort human studies using validated high throughput targeted and discovery assays (#159)

Robert s Plumb 1 , Ian d wilson
  1. Waters Corporation, Milford, MASSACHUSETTS, United States

As global life-styles change we are seeing increasing cases of obesity, diabetes, and mental health issues. This not only affects a person’s quality of life but also places increased strain on the health-care systems to provide the right treatment whilst managing costs closely.

Metabolic Profiling offers a valuable and unique insight into the underlying biochemistry of diseases as well as the patient’s individual biochemistry “phenotype’, diet, health status, age and stress. To deliver this information the analytical data generated in processed via a variety of chemometric modelling and analysis methodologies to deliver the relevant biochemical information. These chemometric platforms employed vary from simple multivariant analysis to highly complex model based analysis and is presented in a format ready for interpretation by medics.

In this presentation we will discuss the development of both exploratory and targeted metabolomics and lipidomic LC/MS analytical platforms as well as a detailed discussion on the workflow, validation, reporting and decision making process. The quantitative targeted LC/MS assays discussed will include as bile acids, amino acids, eicosanoids, and acyl cartanines, oxylipin, tryptophan metabolism and gut microbiome. The presentation will also cover the development and validation of high throughput, less than 2 minutes, “discovery’ screening methods for polar, non-polar metabolites and lipid profiling using LC/MS methodology, as well as describe the use of Ion Mobility Mass Spectrometry to enhance data quality.

  1. Ion mobility spectrometry combined with ultra performance liquid chromatography/mass spectrometry for metabolic phenotyping of urine: Effects of column length, gradient duration and ion mobility spectrometry on metabolite detection. Rainville, P.D., Wilson, I.D., Nicholson, J.K., Issacs, G., Mullin, L., Langridge, J.I., Plumb, R.S. Analytica Chimica Acta Volume 982, 22 August 2017, Pages 1-8
  2. High-Speed Quantitative UPLC-MS Analysis of Multiple Amines in Human Plasma and Serum via Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate: Application to Acetaminophen-Induced Liver Failure. Gray, N, Zi, R., King, A., Patel, V.C., Wendon, J., McPhail, M.J.W., Coen, M., Plumb, R.S., Wilson, I.D, Nicholson, J.K. Analytical Chemistry Volume 89, Issue 4, 21 February 2017, Pages 2478-2487
  3. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies. Gray, N, Adesina-Georgiadis, K, Chekmeneva, E, Plumb, R.S, Wilson, I.D., Nicholson, J.K. Analytical Chemistry Volume 88, Issue 11, 7 June 2016, Pages 5742-5751