Mitesh Sanghvi , Xceleron Inc., A Pharmaron Company, Germantown, MD
Stephen L. English , Xceleron Inc., A Pharmaron Company, Germantown, MD
Ricardo Diaz , Xceleron Inc., A Pharmaron Company, Germantown, MD
Eric Guarin , Xceleron Inc., A Pharmaron Company, Germantown, MD
Marie Croft , Xceleron Inc., A Pharmaron Company, Germantown, MD
The importance of biotherapeutics as a class of drugs has increased significantly over recent years due to their enormous potential in the diagnosis or treatment of a wide array of human diseases ranging from autoimmune and inflammatory diseases to cancer, cardiovascular diseases, and rare genetic disorders. These highly promising therapeutic agents, such as peptides, oligonucleotides, cytokines, and antibody drug conjugates are extremely attractive as drug candidates and these compounds continue to fill the pre-clinical and clinical pipelines of many pharmaceutical companies. With this rapid growth in biotherapies comes increased demand for an analytical platform that is flexible, robust, highly sensitive and easily integrated into pre-existing workflows.

Often found at levels in the sub-ng to low pg/mL range, detection of biotherapeutics requires highly sensitive methods. Currently, a preferred approach for the quantitative analysis of peptide and protein drugs is some combination of an enzymatic digestion, stable isotope labeling, enrichment technique (PPT/LLE/SPE or immunocapture) and analysis using LC coupled with MS (LC-MS). Achieving the sensitivity in high pg to low ng range, along with high specificity employs LC-MS/MS as a routine technology in bioanalysis. While LC-MS/MS technology can still be routinely used for biotherapeutics analysis, emerging uses of high performance liquid chromatography with accelerator mass spectrometry (HPLC+AMS) in biotherapeutics can be considered a valuable tool when lower sensitivity in femtogram (fg) to pg/mL range is required.

The freedom from matrix interference of the AMS detector has been well established. Since the early 1990s, AMS has been used for the quantitative analysis of analytes labeled with 14C in a range of biological matrices. Applications of the technique have progressed from total 14C analysis in mass balance studies to 14C-parent quantitation in microdose and microtracer studies, using HPLC+AMS. Xceleron presents recent examples of the analysis of biotherapeutics using AMS. With the ongoing optimization of sample preparation steps and the emerging use of AMS in the analysis of biotherapeutics, new avenues are opened for translating an increased number of biomarkers and biologics into clinical tests. Furthermore, combined with novel radiolabeling of large molecules, AMS can provide robust analytical quantitation when no other existing analytical technology has sufficient sensitivity to generate these data.