A mass spectrometry method, the method comprising: providing an obtained sample comprising an MHC-I or HLA-I complex or an MHC-II or HLA-II complex and isolating unlabeled peptides from the MHC-I or HLA-I complex or the MHC-II or HLA-II complex to produce a sample comprising unlabeled isolated peptides; adding one or more labeled peptides to the sample to form a single mixed sample comprising the labeled peptides and the unlabeled isolated peptides; processing the single mixed sample with an LC-MS/MS system, comprising: i) processing the mixed sample in discovery mode to detect and identify one or more of the unlabeled isolated peptides and the one or more labeled peptides in the mixed sample; ii) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying unlabeled isolated peptides that have the same retention time as a labeled peptide; iii) wherein, when the labeled peptides are no longer detected, toggling the mixed sample with the LC-MS/MS system into discovery mode to detect and identify unlabeled isolated peptides and labeled peptides in the mixed sample; and iv) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying the unlabeled isolated peptides that have the same retention time as a labeled peptide; wherein the LC-MS/MS system toggles between processing the mixed sample in discovery mode and processing the mixed sample in targeted mode in the same LC-MS/MS run. providing an obtained sample comprising an MHC-I or HLA-I complex or an MHC-II or HLA-II complex and isolating unlabeled peptides from the MHC-I or HLA-I complex or the MHC-II or HLA-II complex to produce a sample comprising unlabeled isolated peptides; adding one or more labeled peptides to the sample to form a single mixed sample comprising the labeled peptides and the unlabeled isolated peptides; processing the single mixed sample with an LC-MS/MS system, comprising: i) processing the mixed sample in discovery mode to detect and identify one or more of the unlabeled isolated peptides and the one or more labeled peptides in the mixed sample; ii) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying unlabeled isolated peptides that have the same retention time as a labeled peptide; iii) wherein, when the labeled peptides are no longer detected, toggling the mixed sample with the LC-MS/MS system into discovery mode to detect and identify unlabeled isolated peptides and labeled peptides in the mixed sample; and iv) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying the unlabeled isolated peptides that have the same retention time as a labeled peptide; i) processing the mixed sample in discovery mode to detect and identify one or more of the unlabeled isolated peptides and the one or more labeled peptides in the mixed sample; ii) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying unlabeled isolated peptides that have the same retention time as a labeled peptide; iii) wherein, when the labeled peptides are no longer detected, toggling the mixed sample with the LC-MS/MS system into discovery mode to detect and identify unlabeled isolated peptides and labeled peptides in the mixed sample; and iv) wherein, when the labeled peptides are detected, toggling the mixed sample with the LC-MS/MS system into targeted mode, thereby detecting and identifying the unlabeled isolated peptides that have the same retention time as a labeled peptide; wherein the LC-MS/MS system toggles between processing the mixed sample in discovery mode and processing the mixed sample in targeted mode in the same LC-MS/MS run.