Development and validation of a targeted affinity-enrichment and LC-MS/MS proteomics approach for the therapeutic monitoring of adalimumab
| Autor: | Kiang-Teck J. Yeo, Eric E. Niederkofler, Kwasi Antwi, Eszter Lazar-Molnar, Emily Wysocki, Yifei Yang, Edward Ki Yun Leung |
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| Rok vydání: | 2017 |
| Předmět: |
musculoskeletal diseases
Drug Proteomics medicine.drug_class media_common.quotation_subject Clinical Biochemistry Biological Availability Pharmacology Monoclonal antibody Antibodies Monoclonal Humanized 01 natural sciences Biochemistry Autoimmune Diseases 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry medicine Adalimumab Humans skin and connective tissue diseases media_common biology business.industry Tumor Necrosis Factor-alpha 010401 analytical chemistry Biochemistry (medical) Therapeutic effect General Medicine medicine.disease humanities 0104 chemical sciences 030220 oncology & carcinogenesis Rheumatoid arthritis biology.protein Tumor necrosis factor alpha Antibody Drug Monitoring business medicine.drug Chromatography Liquid |
| Zdroj: | Clinica chimica acta; international journal of clinical chemistry. 483 |
| ISSN: | 1873-3492 |
| Popis: | Background The anti-tumor necrosis factor alpha (TNFα) therapeutic monoclonal antibodies (mAbs), such as adalimumab, are widely used in the treatment of rheumatoid arthritis, inflammatory bowel diseases, and other auto-immune diseases. The administration of adalimumab can elicit the immune responses from some patients, resulting in the formation of anti-drug antibodies (ADAbs). The ADAbs can diminish the therapeutic effects of adalimumab by neutralizing the TNFα binding site or increasing its clearance from circulation. Methods To effectively monitor the therapeutic concentrations of adalimumab, we developed and validated a targeted quantitative proteomic assay to determine the circulating concentrations of adalimumab. Since drug effects can be attenuated by ADAbs, the method adopted an affinity-enrichment step to selectively quantify the bioavailable forms of adalimumab in patient serum samples. Results The performance of the LC–MS/MS based assay provides the analytical measuring range and precisions applicable for the therapeutic monitoring of adalimumab. It also provides comparable results to a cell-based activity assay when evaluating patient samples with different concentrations of adalimumab. Conclusion Our assay can quantify both sub-therapeutic and therapeutic concentrations of bioavailable adalimumab in patient serum samples. This assay design provides an alternative to isotope-labeled peptides approach currently adopted in targeted proteomics methods. |
| Databáze: | OpenAIRE |
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