Isotopic Ratio Outlier Analysis (IROA) for Quantitative Analysis.

ABSTRACT

There is always a tension within the omics sciences between trying to measure biological molecules rapidly and measuring accurately. Metabolomics as an omics science tries to measure the small biochemicals rapidly, in a single pass, but the current state of the art cannot provide the reproducibility or accuracy needed for clinical use or even daily reproducibility for larger experiments. The IROA TruQuant measurement system uses a daily "Long-Term Reference Standard (LTRS)" and a chemically identical Internal Standard (IS) to provide validated chemical identity, daily QA/QC on instrument and sample preparation, and accurate reproducible quantitation that is comparable across days, instruments, and even, for most compounds, chromatographic methods. The LTRS is, as the name implies, a Long-Term Reference Standard that is always the same and should therefore provide very similar results on a large but finite collection of compounds. All of the compounds in the LTRS are isotopically signed with formula indicating IROA patterns so they cannot be mistaken for one another. Because of the precise IROA patterns, a software-driven analysis of the compounds seen daily can determine the performance of the instrument in terms of sensitivity, in-source fragmentation, and chromatographic and injection stability and provide completely reproducible quantitation.