Development and Validation of Aducanumab by Bioanalytical Method Using Liquid Chromatography-Tandem Mass Spectroscopy

Aducanumab, a monoclonal antibody approved for Alzheimer’s disease treatment, requires precise and reliable quantification in biological matrices for pharmacokinetic studies. We developed and validated a novel high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the sensitive and accurate measurement of Aducanumab in rat plasma. The method demonstrated excellent linearity across the range of 12.50 to 100.00 ng/mL with a correlation coefficient (r²) of 0.999. The limits of detection (LOD) and quantification (LOQ) were established at 2 ng/mL and 5 ng/mL, respectively, indicating the method’s sensitivity. High repeatability was observed with interday and intraday precision values (%RSD) less than 2%. The method also exhibited robust selectivity with minimal matrix effects, and the extraction recovery rates exceeded 95% for all concentration levels tested. Stability studies confirmed the method’s reliability under various conditions, including freeze-thaw cycles and long-term storage. This newly developed LC-MS/MS method offers superior sensitivity, precision, and selectivity compared to previously reported techniques, making it a valuable tool for future pharmacokinetic studies and therapeutic monitoring of Aducanumab in Alzheimer’s disease research. We recommend the method for broader applications in both preclinical and clinical settings due to its robustness and adaptability.