An LC-MS/MS Method for Quantification of Donanemab in Serum
A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing immunoaffinity enrichment to has been developed to quantify donanemab, an Alzheimer’s therapy, in human serum. The process involves immunoaffinity capture followed by tryptic digestion and targeted peptide quantification, and provides a robust, high-precision alternative to traditional immunoassays for monitoring therapeutic monoclonal antibodies in clinical settings.
Monoclonal antibodies hold significant promise for the treatment of Alzheimer's disease (AD), with donanemab being a recent therapeutic human IgG1 antibody approved for clinical use. The development and pharmacokinetic evaluation of antibody drugs necessitate accurate quantification. While immunoassays are currently used mainly by clinical trials to measure those antibody drugs for AD, they often face limitations such as cross-reactivity, insufficient specificity, and poor interlaboratory comparability. In response, researchers at Fudan University and Shanghai AB Sciex Analytical Instrument Trading Co., Ltd. (both in Shanghai, China) have developed a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method which includes immunoaffinity enrichment for serum donanemab. A paper based on this research was published in ACS Omega.1 which states that their method “can effectively distinguish donanemab from endogenous immunoglobulins in serum and have sufficient sensitivity.”