Jordyn A. Moore¹
Specialist Biochemistry, Canterbury Health Laboratories, Health NZ

Proteins are large, complex biomolecules that are essential for cell processes, and are critical biomarkers for disorders and disease. Time-of-flight (TOF) mass spectrometry coupled with reversed phase chromatography is a powerful analytical technique that can provide detailed structural information for intact proteins. Accurate, well resolved protein masses and mass changes can be interpreted to identify proteins and protein variants, post translational modifications including glycosylation, as well as non-enzymatic reactions like glycation. We have implemented several top-down TOF mass spectrometry methods in our laboratory for analysing intact blood proteins. These include variant identification methods for haemoglobin, fibrinogen and albumin, which are used for screening and diagnosis of haemoglobinopathy and thalassaemia, hypo/dysfibrinogenaemia and familial dysalbuminaemic hyperthyroxinaemia (FDH) respectively. As well as methods that focus on interpretation of minor protein masses, such as the glycosylation pattern of transferrin or apolipoprotein CIII, where the structural detail provides a more effective approach to screening a subset of congenital disorders of glycosylation (CDG). Most recently, we validated a glycated albumin TOF mass spectrometry method as an alternative measure of glycaemic control in patients with unreliable HbA1c measurement. In all cases, TOF mass spectrometry has complimented other screening methodologies, or its superiority has changed our laboratory workflow.