BACKGROUND: Recently, the potential of dried blood spots (DBS) for small-molecule bioanalysis by LC-MS has been explored. The goal of this investigation was to evaluate the use of DBS for the quantification of biologics, where bioanalysis is with immunoassay. RESULTS: Therapeutic monoclonal antibodies were successfully eluted from DBS and detected by immunoassays, and the procedure could be validated in alignment with current guidelines. Accuracy, precision, selectivity and dilution linearity were all within the acceptance criteria currently used for the validation of binding assays with serum samples. Serum and DBS samples obtained in parallel during a PK research study in rats were analyzed for drug and anti-drug antibodies using AlphaLISA(®) technology. Drug concentrations in both sample types showed a strong correlation, and there was very good alignment in detection of immunogenicity positive animals. CONCLUSION: Using two examples, we have demonstrated that therapeutic monoclonal antibodies can be accurately quantified in DBS, and since anti-drug antibodies could also be successfully detected, there is scope for application of DBS to preclinical and clinical bioanalysis of monoclonal antibody drugs and anti-drug antibodies.
BACKGROUND: Recently, the potential of dried blood spots (DBS) for small-molecule bioanalysis by LC-MS has been explored. The goal of this investigation was to evaluate the use of DBS for the quantification of biologics, where bioanalysis is with immunoassay. RESULTS: Therapeutic monoclonal antibodies were successfully eluted from DBS and detected by immunoassays, and the procedure could be validated in alignment with current guidelines. Accuracy, precision, selectivity and dilution linearity were all within the acceptance criteria currently used for the validation of binding assays with serum samples. Serum and DBS samples obtained in parallel during a PK research study in rats were analyzed for drug and anti-drug antibodies using AlphaLISA(®) technology. Drug concentrations in both sample types showed a strong correlation, and there was very good alignment in detection of immunogenicity positive animals. CONCLUSION: Using two examples, we have demonstrated that therapeutic monoclonal antibodies can be accurately quantified in DBS, and since anti-drug antibodies could also be successfully detected, there is scope for application of DBS to preclinical and clinical bioanalysis of monoclonal antibody drugs and anti-drug antibodies.
Authors: Sophie E Berends; Geert R A M D'Haens; Tiny Schaap; Annick de Vries; Theo Rispens; Karien Bloem; Ron A A Mathôt Journal: Br J Clin Pharmacol Date: 2019-05-11 Impact factor: 4.335