Capture reagents are critical to affinity-based bioanalytical methods. The potential bias of capture reagents, for or against certain subpopulations of the target of interest, may lead to inaccurate quantitation. This issue is more profound for sensitive measurements, such as post-translational modification (PTM) profiling of therapeutic proteins from complex matrix. Here, a recently developed affinity purification coupled mass spectrometric method was utilized to assess the full sequence of a circulating therapeutic aglycosylated IgG1 (MAB3) in human subject, using two different capture reagents. We monitored all PTMs known to be related to MAB3 drug quality (three representative PTMs are shown in this paper). The results validated the comparability of these two reagents.