MS methods for measuring monoclonal protein. There are 2 types of MS methods in clinical use. The top-down, intact light-chain approach uses, for example, MALDI to prepare the sample for MS analysis and then relies on the monoclonal protein’s unique m/z ratio to distinguish itself from the polyclonal background. Examples include Mass-Fix and Exent. To increase sensitivity, samples that initially test negative can then be directed to LC-MS; this is under evaluation on a research basis. In the bottom-up, clonotypic approach, the monoclonal protein is digested and a unique clonotypic sequence then determined to use for tracking the monoclonal protein. This method is more sensitive than the top-down approach but has a slower turnaround time and requires a baseline sample for the sequence to track. The EasyM and M-Insight assays use the clonotypic approach.