Dr Keith Mulready

Chief Medical Scientist

Mater Misericordiae University Hospital

Biography

Presentation Title: “Development and Validation of salivary biomarkers utilising Liquid Chromatography-Tandem Mass Spectrometry”

Abstract: 

The use of saliva has provided a substantial addition to the diagnostic armamentarium as an investigative tool for disease processes and disorders. Measurement of salivary cortisol and its inactive metabolite cortisone is a viable alternative to conventional serum cortisol measurements. Salivary cortisol/cortisone are in the free unbound physiologically active form and are unaffected in conditions affected by protein binding such as oestrogen therapy and acute illness.

Owing to very low physiological levels of salivary steroids, a highly sensitive, specific and selective method is required for accurate and precise quantification. Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) provides this diagnostic modality, measuring an analyte by its specific mass-to-charge ratio and can alleviate inherent methodological flaws with immunoassays e.g. cross-reactivity.

The development and validation of a novel mixed-mode anion exchange solid phase extraction LC-MSMS method also requires the establishment of appropriate normal reference intervals and receiver operator characteristic curves/diagnostic cut-off values in pathological conditions to enable clinical translation. This method can be utilised for screening and diagnosis of various Hypothalamic-Pituitary-Adrenal disorders. The midnight salivary cortisol reference interval devised using this method can be applied in the diagnosis of Cushing’s Syndrome as recommended by the Endocrine Society Clinical Practice Guidelines or as a favourable alternative in the assessment of adrenal hypofunction (adrenal insufficiency) during the dynamic function test, Synacthen test, replacing conventional serum cortisol with salivary cortisol/cortisone over the three-time-points.

Speaker Bio:

Keith Mulready is a Chief Medical Scientist in the Clinical Chemistry and Diagnostic Endocrinology Laboratory, Mater Misericordiae University Hospital, Dublin. Keith attained his BSc. in Biomedical Science from D.I.T Kevin St, MSc. from the University of Ulster and post graduate qualifications in LC-MSMS from the University of Greenwich.

He has worked as a Specialist in the field of clinical Liquid Chromatography-Tandem Mass Spectrometry (LC-MSMS) since 2009. He has a key role in the method development and validation of this service encompassing esoteric testing and test repatriation which provides a platform for the Mater as a National referral centre. Keith attained his PhD in Medicine, School of Medicine, University College Dublin, specialising in the development and clinical validation of novel biomarkers utilising LC-MSMS under the principal supervision of Professor Maria Fitzgibbon, Consultant Clinical Biochemist.