GEN-MKT-18-7897-A
Jan 10, 2017 | Biopharma, Blogs | 0 comments
Protein-based biotherapeutics, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are a growing component of pharmaceutical companies’ drug pipelines. The growth of ADCs in particular is due to their ability to selectivity target and deliver a potent molecule to a cancer cell based on a specific tumor marker. In order to support this growing class of new drug molecules, robust and reliable bioanalytical methods are required. While ligand binding assays (LBAs) like ELISA have been the most popular platform for biotherapeutic quantitation, bioanalytical scientists have been increasingly adopting hybrid LBA/LC-MS methods in this area.
The strengths of hybrid LC-MS assays for this application include:
For a bioanalytical scientist inexperienced in hybrid LBA/LC-MS signature peptide quantitation, the various workflows can appear complex and difficult. BioBA sample preparation kits are designed to make this complex process simple by enabling a magnetic bead-based approach to immunoaffinity sample preparation and providing all the reagents necessary (buffers, reagents, enzyme and bead) to complete the workflow.
Most ADCs are heterogeneous mixtures of species and an example is ado-trastuzumab emtansine, a lysine-linked ADC that is an approved treatment for patients with Her2+ breast cancer. The nature of the chemistry involved in lysine conjugation makes the drug product a heterogeneous mixture of species with a drug to antibody (DAR) of 0 to 8. The heterogeneous character of ADCs like adotrastuzumab emtansine require several bioanalytical assays during the drug development process. Some of these include:
Hybrid LBA/LC-MS assays can be used to address conjugated and total antibody assays by choosing an appropriate immunocapture reagent. An anti-payload antibody can be used to immunopurify and assay conjugated ADC species. To assay the total antibody, a generic anti-human Fc antibody can be employed for immunocapture, or a target-specific immunocapture strategy can be employed with recombinant target protein or an anti-idiotype antibody.
Download the tech note to see a full demonstration of a total antibody assay of ado-trastuzumab emtansine using hybrid LBA/LC-MS approach employing the BioBA sample preparation kit and a generic immunocapture strategy.
The Echo® MS+ system is a novel platform for Acoustic Ejection Mass Spectrometry (AEMS) and combines the speed of acoustic sampling with the selectivity of mass spectrometry. This platform has been designed for high throughput analysis of small and large molecules. The technology combines Acoustic Droplet Ejection (ADE), an Open Port Interface (OPI) and could be coupled with the SCIEX Triple Quad 6500+ system or the ZenoTOF 7600 system.
The Echo® MS+ system comprises of an open-port interface (OPI) and acoustic droplet ejection (ADE) module which could be coupled with a mass spectrometer. The mass spectrometer could either be a SCIEX Triple Quad 6500+ system or the ZenoTOF 7600 system. This non-liquid chromatography based; high-throughput screening platform enables rapid analysis of compounds at speeds of up to 1 sample/second.
The ability to consistently achieve reproducible results on many complex samples across multiple days is critical to a routine clinical laboratory. Laboratories relying on analytical instrumentation require stability and robustness to perform a variety of screening and confirmatory assays with confidence. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the preferred analytical method in the clinical laboratory to reliably perform clinical testing as it provides best-in-class performance and reliability for the most challenging assays. LC-MS/MS offers the required levels of sensitivity and specificity for the detection and quantitation of molecules from complex biological samples, helping laboratories deliver highly accurate data for a variety of clinically relevant analytes across a wide range of assays.
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