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Targeted Metabolite Analysis

Metabolite analysis has traditionally been directed at specific metabolites, metabolic pathways, drugs or toxins of known biological or clinical significance. Our group is interested in developing robust CE and CE-MS methods for reliable analysis of metabolites or electrolytes that offer major advantages for routine screening, including higher sample throughput, greater selectivity and lower detection limits. This work applies fundamental aspects of separation science for the development of assays that enable accurate quantification of metabolites in biological samples (e.g., urine, plasma, stool, sweat, tissue extracts) that are low often difficult to measure by conventional methods. We place strong emphasis on application of experimental design for method optimization, as well as rigorous method validation studies (including proficiency testing and ring trials) that includes implementation of quality controls. Recent efforts towards expanded drug analysis using our multiplexed CE-MS technology offers a cost-effective solution for drug surveillance and therapeutic monitoring of high-risk patients given the alarming opioid crisis in North America.

Figure 1-Targeted Metabolite Analysis

Fig. 1. Overview of a multiplexed CE-MS method that makes use of temporal signal pattern recognition for reliable quantification of biomarkers for confirmatory testing of rare genetic diseases from a single dried spot cut-out extract in support of universal newborn screening programs.

Figure 2-Targeted Metabolite Analysis

Fig. 2. Overview of a validated CE-UV assay for urinary iodide that includes on-line preconcentration via sample stacking and dynamic inclusion complexation as required for continuous monitoring of iodine deficiency in epidemiological studies.

 

Recommended references:

  1. A. DiBattista,* D. Rampersaud, H. Lee, M. Kim and P. Britz-McKibbin “A High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry” Anal. Chem. 2017, 89, 11853-11861[Editor’s choice] 
  2. A. DiBattista,* N. McIntosh, M. Lamoureux, O.Y. Al-Dirbashi, P. Chakraborty and P. Britz-McKibbin “Temporal Signal Pattern Recognition in Mass Spectrometry: A Method for Rapid Identification and Confirmatory Testing of Biomarkers for Inborn Errors of Metabolism with Quality Assurance” Anal. Chem. 2017, 89: 8112-8121.
  3. A. Nori de Macedo,* J. Macri, P.L. Hudecki, M. Saoi,* M.J. McQueen, and P. Britz-McKibbin “Validation of a Capillary Electrophoresis Assay for Monitoring Iodine Nutrition in Populations: An Inter-laboratory Method Comparison” J. Appl. Lab. Med.2017, 2:649-660.
  4. S. Fernando,* M. Gallea,* L. VandenEnden,* R. House, D.K. Verma, L. Shaw, D. Shaw,  B.E. McCarry and P. Britz-McKibbin “Evaluation of Firefighter Exposure to Wood Smoke During Training Exercises at Burn Houses” Environ. Sci. Technol. 2016, 50:1536-1543.