Quetmolimab

E6011 is a novel monoclonal antibody developed for the treatment of rheumatoid arthritis. Ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) has become increasingly important in the assays of therapeutic antibodies, yet achieving high sensitivity remains a major challenge. For the E6011 assay, an immunoaffinity (IgG-IA) method employing protein G in combination with UPLC-MS/MS was utilized and qualified in monkey serum. Method development revealed that increasing the matrix volume did not always lead to improved sensitivity when using a fixed volume of protein G magnetic beads, due to their limited capture capacity. Using only 1.8 µL of monkey serum, E6011 was quantitatively analyzed at concentrations as low as 1 µg/mL. Accuracy and precision were within ±20 %, meeting the acceptance criteria, however, the selectivity result at 1 µg/mL highlighted the need for evaluation of selectivity across multiple individuals. E6011 concentrations in monkey serum were determined using the IgG-IA-UPLC-MS/MS method, and the resulting pharmacokinetic parameters were comparable to those previously reported using UPLC-MS/MS with ammonium sulfate precipitation and a ligand-binding assay. These findings highlight the importance of optimizing matrix volume in assay development and demonstrate the successful application of the established method in a monkey pharmacokinetic study.