MSACL 2026 Abstract

Tips and Tricks for Developing Tests for the Quantitation of Therapeutic Monoclonal Antibodies

Paula Ladwig, Mindy Kohlhagen
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN

Paula Ladwig, MS, MLS(ASCP) (Presenter) Mayo Clinic

Presenter Bio: Paula M. Ladwig, MS, MLS(ASCP), is a Principal Developer with the Clinical Mass Spec Development Laboratory and an Assistant Professor in the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, MN. She has over 15 years of experience in LC-MS LDT development and validation. Her interests include the implementation of therapeutic drug monitoring of monoclonal antibody therapeutics by LC-MS methods.

Relevant Financial Disclosures (within past 24 months, reported on Feb 27, 2026) No relevant financial relationship(s) to disclose.

To provide best practices for development, validation and implementation of MS methods for the quantitation of therapeutic monoclonal antibodies (tmAbs). The goal of this session is not to provide method specific details from our published methods, but instead to share the lessons learned as we streamlined our pipeline for TDM for new tmAbs. Multiple methods have been utilized for the enrichment of tmAbs to include enriching either all immunoglobulins, a class or subclass, or for a specific antibody. Automation efficiencies has been implemented at various stages. Detection has included either peptide or light chain from the tmAb of interest. Instrumentation has spanned MALDI for screening to single or multiplex HPLC systems connected to either a triple quad, orbitrap or time of flight MS for quantitation. The speakers will share some of the headaches, best practices and innovations of being at the forefront of a new analyte, extraction method or platform.

Take Home Pearls:

1. Describe best practices that improve assay accuracy and precision, including matrix selection, internal standard usage, and selection of appropriate reference materials.
2. Explain how antibody type (chimeric, humanized, subclass specific) influences method selection for clinical therapeutic drug monitoring.
3. Identify key factors that determine appropriate enrichment and detection strategies for quantitating therapeutic monoclonal antibodies using mass spectrometry.
4. Differentiate the advantages and limitations of peptide based versus intact light chain mass spectrometric detection across available instrument platforms (triple quad, orbitrap, TOF, MALDI).
5. Outline a streamlined development pathway for implementing new monoclonal antibody quantitation assays in a clinical laboratory setting.