Use of an alternative signature peptide during development of a LC-MS/MS assay of plasma nivolumab levels applicable for multiple species

Recently, immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1) antibodies, have dramatically changed treatment strategies for several cancers. In pharmacokinetic/pharmacodynamic studies, experiments using a variety of animal species are assumed. We identified optimal multiple reaction monitoring transitions signature candidate peptides nivolumab in human, mouse, and rat plasma developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify (an anti-PD-1 antibody) trastuzumab as the internal standard. Calibration curves were linear range 1–200 µg/mL. The intra- inter-day precision accuracy human fulfilled Food Drug Administration guideline criteria bioanalytical validation. There was no need change measurement mouse plasma. On other hand, plasma, an interference peak observed at retention time similar that surrogate peptide ASGITFSNSGMHWVR (550.75 > 661.50) employed Therefore, we confirmed ASQSVSSYLAWYQQKPGQAPR (785.0 940.2) can be used alternate same concentration Using our method, gradual increase trough value clinical samples from two antibody-treated patients, one with gastric cancer non-small-cell lung cancer. course blood transition also evaluated administration rat. present study showed selection is essential accurate LC-MS/MS here expected use non-clinical pharmacokinetic studies.