Liquid Chromatography
Mass Spectrometry (LCMS)

At BioAnalysis, we provide expert cGMP mass spectrometry services designed to support the full lifecycle of biologic therapeutics, viral vectors, mRNA drugs, and lipid nanoparticle (LNP) formulations. This technology is an emerging best practice because it offers precise identification of proteins of interest, plus structural and functional modifications that impact gene therapies, mAbs, and other emerging modalities. 

LCMS is a powerful technology that allows for peptide mapping, analysis of post translational modifications, and intact mass analysis for complete characterization of viral capsids, oligos, antibodies, and cellular proteins.  Our services span method development, qualification, and validated release testing, delivering high-resolution data fully compliant with regulatory expectations for IND and BLA filings.  The BioAnalysis LCMS SME team is well versed in protocols characterizing relevant modifications and protein profiles across diverse modalities, from discovery stages to commercial release testing. 

With advanced instrumentation, including the ThermoFisher Orbitrap Exploris 480 and AB Sciex X500b QTOF, clients can expect unparalleled accuracy in analyzing identity, purity, structure, and stability across complex biological therapeutic modalities.  These instruments, along with our ability to run LCMS analyses in GMP, are crucial for assessing the critical quality attributes of biologic drug products

Popular Applications

Peptide Mapping

The primary amino acid sequence of the capsids in your Gene Therapy, manually verified by BioAnalysis Subject Matter Experts.

  • Verifies complete primary amino acid sequence coverage
  • For viral capsids like AAV, it can be used to identify sequence variations specific to different serotypes or recombinant capsids.
  • For gene therapy potency, measure gene of interest expression in target cells

Intact Mass

Assess capsid protein (VP1:VP2:VP3) ratios and capsid molecular weights. Intact mass provides a mass accuracy accurate to the low parts per million (ppm) range.

  • Confirms protein identity and molecular weight to low part-per-million accuracy
  • Detects capsid truncations, isoforms, and glycoform heterogeneity
  • Assesses AAV capsid composition, including VP1:VP2:VP3 ratios
  • Supports GMP release testing, comparability, and stability studies

Host Cell Protein (HCP)

Rely on stringent MS/MS evaluation, relative and consistent quantitation, and in-depth analysis of the identified HCPs.

  • Uses high-resolution MS/MS proteomics to identify and quantify residual host cell proteins from cellular production systems (HEK, CHO, SF9)
  • Tracks HCP clearance during purification
  • Supports cell line evaluation
  • Enables differential protein profiling across process conditions or production batches
  • Relative and consistent quantitation

Post Translational Modifications (PTMs)

In addition to serotype sequence information, post-translational modifications are identified and quantified to inform gene therapy critical quality attributes.

  • Identify site-specific PTMs like deamidation, oxidation, phosphorylation, methylation, ubiquitination, acetylation, etc.
  • Used to understand stability, function, and safety of advanced biologics like monoclonal antibodies and protein-based drugs.
  • Changes in PTMs are linked to changes in aggregation and binding affinity which can result in increases in immunogenicity and/or reduced biological function for the therapeutic. 

Additional LCMS capabilities

Therapeutic mRNAs, Guide RNAs, Lipid Nanoparticles (LNPs), Vaccine Characterization

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Native Mass Spectrometry for Complex Assemblies

  • Analyzes multimeric complexes, viral particles, and conjugated biologics in non-denaturing conditions
  • Preserves native structure for accurate drug-to-antibody ratio (DAR), capsid assembly, or LNP-cargo profiling
  • Supports characterization of ADCs, AAV vectors, and mRNA-LNP therapeutics
  • Reveals biologically relevant conformations and aggregation behavior

Quantitation of mRNA, Proteins, and Payloads

  • Provides absolute or relative quantitation of mRNA, gRNA, proteins, peptides, and viral capsid proteins
  • Accurately calculates DARs, mRNA payload concentrations, and capsid-to-genome ratios
  • Critical for establishing dose accuracy, potency, and batch consistency
  • Essential for release testing of LNP-based RNA therapeutics and biologics

Proteomics

  • Determines global changes in protein levels due to changes in expression or degradation
  • Provides a protein fingerprint reflective of changes in conditions (media, cellular, etc)
  • Can be used to screen for protein degraders, identify new drug targets, monitor mechanisms of action for therapeutics, and many other applications

Limited Proteolysis to Study Protein Flexibility

  • Identifies surface-exposed or flexible protein regions
  • Reveals structural changes upon drug binding, conjugation, or formulation stress
  • Supports epitope mapping, ADC site characterization, and protein engineering
  • Provides insights into protein folding, accessibility, and conformational dynamics