Accurate Clinical Detection of Vitamin D by Mass Spectrometry: A Review

Vitamin D deficiency is thought to be associated with a wide range of diseases, including diabetes, cancer, depression, neurodegenerative diseases, and cardiovascular and cerebrovascular diseases. This vitamin D deficiency is a global epidemic affecting both developing and developed countries and therefore qualitative and quantitative analysis of vitamin D in a clinical context is essential. Mass spectrometry has played an increasingly important role in the clinical analysis of vitamin D because of its accuracy, sensitivity, specificity, and the ability to detect multiple substances at the same time. Despite their many advantages, mass spectrometry-based methods are not without analytical challenges. Front-end and back-end challenges such as protein precipitation, analyte extraction, derivatization, mass spectrometer functionality, must be carefully considered to provide accurate and robust analysis of vitamin D through a well-designed approach with continuous control by internal and external quality control. Therefore, the aim of this review is to provide a comprehensive overview of the development of mass spectrometry methods for vitamin D accurate analysis, including emphasis on status markers, deleterious effects of biological matrices, derivatization reactions, effects of ionization sources, contribution of epimers, standardization of assays between laboratories.