Electrospray ionisation mass spectrometry: principles and clinical applications.

TLDR

ESI‑tandem mass spectrometry is valuable for screening metabolic disorders, generating cluster ions for macromolecule structure elucidation, and is expected to shape future clinical laboratory services. This mini‑review aims to provide a general understanding of electrospray ionisation mass spectrometry (ESI‑MS) as an increasingly important technique for structural study and quantitative measurement of metabolites in complex biological samples. The review explains the electrospray ionisation process, mass‑spectrometer design, spectrum characteristics, quantitative analysis considerations, and discusses clinical applications. ESI‑MS enables improved identification of haemoglobin variants, supports an IFCC reference method for HbA1c, and advances standardisation of diabetic monitoring.

Abstract

This mini-review provides a general understanding of electrospray ionisation mass spectrometry (ESI-MS) which has become an increasingly important technique in the clinical laboratory for structural study or quantitative measurement of metabolites in a complex biological sample. The first part of the review explains the electrospray ionisation process, design of mass spectrometers with separation capability, characteristics of the mass spectrum, and practical considerations in quantitative analysis. The second part then focuses on some clinical applications. The capability of ESI-tandem-MS in measuring bio-molecules sharing similar molecular structures makes it particularly useful in screening for inborn errors of amino acid, fatty acid, purine, pyrimidine metabolism and diagnosis of galactosaemia and peroxisomal disorders. Electrospray ionisation is also efficient in generating cluster ions for structural elucidation of macromolecules. This has fostered a new and improved approach (vs electrophoresis) for identification and quantification of haemoglobin variants. With the understanding of glycohaemoglobin structure, an IFCC reference method for glycohaemoglobin assay has been established using ESI-MS. It represents a significant advancement for the standardisation of HbA1c in diabetic monitoring. With its other applications such as in therapeutic drug monitoring, ESI-MS will continue to exert an important influence in the future development and organisation of the clinical laboratory service.