Proteins and peptides represent a growing class of therapeutics due to their target specificity, lower toxicity, and higher potency. Historically, monoclonal antibodies have been quantified using (LBAs). Recently there has been a trend toward increased analysis using LC-MS, which offers the benefits of multiplexing, improved specificity, broader linear dynamic range, and faster method development times. In addition, LC-MS avoids common LBA shortcomings such as cross reactivity and anti-drug antibody effects in the assay. However, quantification of proteins by LC-MS is not without its challenges. There is no single standardized workflow and the multitude of workflow options can make it difficult to know where to obtain optimal results.