Our findings clearly demonstrate that our strategy is well-suited to reliably and precisely assess the ssDNA content in AAV products by determining vector's subpopulations (empty, filled, and with two short genomes). Along with nSEC, CD-MS provides detailed information about AAV8 content and structure. Our nSEC strategy can separate the AAV monomeric assembly from its oligomers, higher-order aggregates, and low molecular weight fragments. While MALS enabled the detection of low abundant AAV8 oligomers and higher order aggregates, CD-MS distinguished truncated from full-length versions of AAV8 assemblies. This reflected the high degree of complementarity between these two strategies. Aggregation and truncation in AAV formulations are problems of significant concern, affecting the safety and efficacy of AAV-based gene therapies . Analysis of the fractions containing AAV8 oligomers and higher order aggregates by CD-MS revealed that AAV aggregates carry a significant portion of therapeutically irrelevant empty capsids. Identification of empty AAV capsids is of key importance for the development and production of AAV-based therapies. In addition to contributing to the total viral load without providing any therapeutic benefit, empty capsids might overestimate the therapeutic potency of AAV-based therapies because the total particle count might not accurately reflect the number of functional AAV capsids. During clinical dosage, empty vectors add to the total viral load, and capsid-triggered immune responses might be worsened by increased viral loads . Regardless of their value, over-filled, filled, and empty capsids must be closely monitored to ensure the quality and efficacy of AAV-based therapeutics. This workflow enables quality and structural assessments of AAV products, and its implementation can guide AAV production for the safety and efficacy of AAV-based drugs.