The suitability of a liquid chromatography–high-resolution mass spectrometry (LC–HRMS) method for monitoring peptide drug product quality is demonstrated on three case studies using the peptide drugs salmon calcitonin, bivalirudin and exenatide as model systems. LC–HRMS methods were able to provide qualitative information by characterizing the peptide structure and sequence and identifying peptide-related impurities. In addition, LC–HRMS methods can be used to obtain quantitative results with high selectivity, sensitivity, accuracy and precision and suitable linearity. Furthermore, LC–HRMS methods are advantageous because they have the ability to separate and detect low-level impurities where traditional high-performance liquid chromatography–UV detection (HPLC–UV) methods can lack the necessary specificity and sensitivity. Overall, LC–HRMS is an approach that can be used as part of the analytical framework to ensure proper quality control of peptide drug products including the assessment of peptide-related impurities.