Key Manufacturers: Waters
Xevo CDMS
The Xevo CDMS is a charge detection mass spectrometry system designed to measure the mass of very large and heterogeneous biomolecules at the single-particle level. It captures the charge and the m/z of each ion independently, which allows the instrument to calculate a true mass for every detected particle.
This system is useful for AAV capsid analysis, LNP mass profiling, VLP characterization, plasmid structural assessment, and studies of large protein complexes. It is typically used during characterization, method development, and comparability work where direct mass information helps clarify complex sample populations.
The instrument supports very small sample volumes, produces clear mass distributions, and can detect species across a broad mass range—from protein assemblies to virus-sized particles.
Key Capabilities
Direct measurement of megadalton-scale species without relying on deconvolution or narrow charge-state distributions.
Particle-by-particle mass analysis, enabling the detection of heterogeneous or mixed populations.
Quantification of AAV empty/full ratios from intact particles.
Assessment of LNP and VLP mass distributions, useful for comparability and formulation development.
Characterization of protein/oligonucleotide conjugates, including degree-of-conjugation (DoC) insights not easily accessible by LC-MS.
Why this instrument is useful in CMC work:
It helps clarify population shifts during upstream or downstream changes and provides an orthogonal confirmation of capsid content distributions. For LNPs and VLPs, the mass profile can reveal formulation effects that are not obvious in other assays.
While the system offers clear mass-based information, it is currently more suited for characterization than routine QC. Throughput and sample preparation requirements remain factors to consider when placing CDMS into analytical workflows.
Official Websites & Resources
- Waters Xevo CDMS (www.waters.com)
Associated Analytical Procedures
Context in Practice: Example Specifications
From: Typical AAV Drug Product Specifications
This instrument is used in the context of measuring the Quality Attribute Capsid Empty/Full Ratio with the following details:
- Purpose / Rationale: A key purity and potency attribute, as only full capsids are therapeutically active.
- Typical Acceptance Criteria: The specification is product-specific and justified by clinical and manufacturing data. It is typically set as a minimum percentage of full capsids (e.g., NLT 25%) or a maximum percentage of empty capsids (e.g., NMT 75%).
