Development of a 25-Hydroxyvitamin D Liquid Chromatography-Tandem Mass Spectrometry Assay, Cleared by the Food and Drug Administration, via the De Novo Pathway

Despite great improvement in vitamin D assay standardization, inaccurate recoveries of 25(OH)D-2 remain for immunoassays, and many laboratory developed LC-MS/MS methods do not separate out the 3-epimer interferents. Through the process of obtaining Food and Drug Administration (FDA) clearance, we learned that communication is key. Mass spectrometry-based assays raise different questions of safety and efficacy than the predicate immunoassays, with fewer risks due to increased accuracy. This process required improving our quality management system to support the development and registration of an in vitro diagnostic device. There are similar examples for a number of analytes, requiring expeditious entry of FDA-cleared LC-MS/MS methods into clinical laboratories.