Assay for thyroid hormone diagnostics by direct injection-tandem mass spectrometry

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This project aims to develop a simple, selective yet ultra-sensitive assay to measure thyroid hormones in human blood by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in partnership with a local Canadian instrument manufacturer, Ionics Mass Spectrometry. Thyroid hormone status is widely measured in clinical laboratories in the context of newborn screening, as well as diagnostic testing and treatment monitoring of various acquired thyroid related-diseases (e.g., hypothyroidism) that impact human health and quality of life. Currently, thyroid hormones are measured by fluorescence-based immunoassays that lack adequate selectivity resulting in bias and high rates of false-positives. There is an urgent need for alternative methods that offer improved reliability and lower operating costs for routine testing of thyroid function in a clinical setting. However, due to its extremely low concentration levels and inherent instability, direct analysis of thyroid hormones by ESI-MS/MS is challenging due to plasma interferences that result in ion suppression. We propose to introduce an improved strategy for free and/or protein-bound thyroid hormone analysis based on a novel sample cleanup and sensitivity enhancement protocol prior to direct injection-ESI-MS/MS. Method optimization will take place in our laboratory at McMaster University followed by its translation at Ionics Mass Spectrometry for subsequent validation. This timely project will provide a rapid yet cost-effective clinical application of MS/MS technology for routine diagnostic testing of thyroxine hormone status without low throughput chromatographic separations that will improve patient care based on early detection of treatable thyroid related-disorders.