15 March 2013

AMS provides a universal method for quantitation of biologics, ADCs and large molecules in preclinical development

Biologics and other large molecules pose difficult quantitative challenges to existing analytical methods of detection. Accelerator Mass Spectrometry (AMS) addresses the limitations intrinsic to LC/MS/MS and immunoassays. Further, AMS is ideally suited to solving technical problems unique to biologics, antibody-drug conjugates (ADCs) and other large molecules in discovery and early stage development when time-dependent decisions are most critical.

Major Benefits Include:

Simple Chemistry: Through incorporation of a single heavy carbon tag (14C) using simple ligation chemistries or intrinsic growth labeling with 14C-amino acids, a labeled and intrinsically active large molecule is quantified to attomolar concentrations with predictable and universal LLOQs.

Universal Assay: The assay is independent of molecular structure and universally applicable without antibody production or discovery of signature peptides. Heterogeneity in forms, modifications in structure, and/or changes to the payload molecule (in ADCs) do not alter the LLOQs. When the payload molecule is labeled in ADCs uptake and release at the target cell or receptor can be confirmed early in development.

Supporting Other Analytical Tools: The AMS methodology will provide kinetic, biodistribution, ADME, and cellular targeting information prior to or during ELISA and LC/MS development, thus enabling confident decision making. This information will further help guide development of traditional assays, providing an absolute benchmark for the bioanalytical chemist.

Key features of AMS bioanalysis assays that contribute to reduced overall time when compared to standard techniques include the following:

• No compound specific method development
• Absolute and linear quantitation without calibration standard
• Femto- to attomolar sensitivity with <3% repeat measurement imprecision
• Quantitation is independent of matrix or molecular structure
• Simple labeling chemistries can be performed on bench top using established reagents
• Ambient levels of ¹⁴C

Eckert & Ziegler Vitalea Science (EZVS) delivers the fastest turnaround times in the industry. Through a network of qualified providers, we can assist from study design to data interpretation to assure studies have positive outcomes. The following services are offered in conjunction with established alliances:

• Preclinical facilities and Phase 0/I clinics around the world
• Radiolabeling
• Formulations
• Complementary quantitative and qualitative bioanalytical testing
• Pre-study consultation with every contract

Related EZVS Presentations and Publications include:

"Matrix independent quantitation of proteins to attomole levels in milligram-sized samples", Dueker S, Hoffman A, Abidi S, Vogel J, Poster presentation at ASMS 2012

"Quantitative analysis of proteins by accelerator mass spectrometry", Dueker S, Presentation at DVDMDG April 2012

"Accelerator mass spectrometry in protein analysis", in Kamp, RM, Calvete, JJ, Choli-Papadopoulou, T (eds.), Proteome and Protein Analysis, pp. 203-215. Berlin: Springer-Verlag. John S Vogel, Darren J Hillegonds Magnus Palmblad, Patrick G. Grant and Graham Bench (2004)

"Attomole level protein sequencing by Edman degradation coupled with accelerator mass spectrometry", PNAS/dgi/doi/10.1073/pnas.071047998, Miyashita M, Presley J, Buchholz B, Lam K, Lee Y, Vogel J, Hammock B. (2001)

For a comprehensive list of publications and presentations, please visit the EZVS website http://www.vitaleascience.com or contact Ann Hoffman: ann.hoffman@ezag.com, +1 801-706-2237.

If you have questions or are interested in receiving more information pertaining to the analytical capacity of AMS and associated methods, please contact us. We look forward to speaking with you at one of the following events in the coming months:

April 8th - 11th, 7th WRIB Workshop on Recent Issues in Bioanalysis, Long Beach, CA
Poster: Achieving Regulatory Approval for Accelerator Mass Absolute Bioavailability Studies, Stephen Dueker, et.al.

June 9th - 13th, 61st ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, MN

About Eckert & Ziegler Vitalea Science

Eckert & Ziegler Vitalea Science (EZVS) is an integrated provider of isotopes and isotope measurement and calibration services. Our Davis, California facility is dedicated to GLP-level bioanalysis and was founded in 2003, by researchers from the University of California. EZVS is the first U.S.-based bioanalytical contract research organization dedicated to providing services for exploring the pharmacokinetics and metabolism of drug candidates directly in humans and non-clinical species using AMS, both prior to and as part of phase I clinical trials. EZVS prides itself in utilizing the BioMICADAS, the only AMS instrument purpose-built to address the specific needs of the pharmaceutical industry.

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