Vitamin D metabolite quantitation by LC-MS/MS

Rickets as a pathological entity has been known since the archaic times but the first scientific description of rickets dates back to the late 1600s. It was not until the early 1920s that findings demonstrating that rickets could be cured with "accessory'' food nutrients or by exposing affected children to ultraviolet (UV) light were published. These groups of accessory food nutrients also shown at that time, to cure scurvy by feeding fresh vegetables to sea-faring sailors were termed as vital amines or vitamins by Casimir Funk. McCollum and Edward Mellanby classified vitamins into water or fat soluble compounds and showed that cod liver oil contained the antirachitic compound that could cure experimental dogs made to acquire rickets by restricting sunlight exposure. This fat-soluble antirachitic substance, shown to be different than vitamin A by McCollum, was named as vitamin D. Orr in 1923 demonstrated that vitamin D stimulates intestinal absorption of calcium, whereas Shipley and Holtrop's work in 1926 showed that bone mineralization is promoted by an increased plasma calcium and phosphate concentrations directly regulated by vitamin D. The findings that vitamin D has to be metabolically activated to exert its calcemic effects and that it also plays a rather counter-intuitive role on calcium resorption from bone in presence of parathyroid hormone (PTH) were established during 1950-70. In the decades that followed the scientific literature witnessed an exponential growth in the understanding of vitamin D biochemistry along with the advent of advanced quantitative tools including radio immunoassays (RIAs), which helped isolate and quantitate vitamin D and its metabolites with high degree of accuracy.