bioanalysis
CASE STUDY
Expert Voice: Andy Xue
Strategies for ADC Bioanalysis: Building for Complexity, Designing for the Future
Originally recorded at AAPS PharmSci 360, 2025 | Bioanalysis Zone
Meet Andy Xue
Andy Xue is a bioanalytical scientist at Resolian with a specialism in complex modalities, including antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), and antibody-oligonucleotide conjugates (AOCs). His path into the field began with LC-MS work during his Masters in Chemistry and has since taken him through the expanding frontier of targeted conjugate therapies.
In this interview, recorded at AAPS PharmSci 360 2025, Andy talks with Bioanalysis Zone about what makes ADC bioanalysis uniquely demanding, how Resolian approaches scalability across drug development phases, and how the team stays ahead of rapidly evolving linker and conjugation technologies.
Watch the interview: Strategies for ADC Bioanalysis: An Interview with Andy Xue
Why ADC Bioanalysis Is a Different Problem
ADCs combine an antibody, a linker, and a highly toxic payload. That structural complexity translates directly into bioanalytical complexity. As Andy explains, FDA guidance requires measurement of free payload, total ADC, total antibody, and anti-drug antibodies at minimum, with further assays potentially needed depending on mechanism of action.
This is a fundamentally different challenge compared to small molecules or peptides, which follow well-established LC-MS workflows. Andy outlines the key decision points when approaching ADC method development:
- Platform selection: LC-MS versus ligand-binding assay (LBA) is the first fork in the road. The right answer depends on the specific analyte and the sensitivity required.
- Linker chemistry: most ADCs use cleavable linkers, requiring careful sample preparation to prevent premature breakdown. Non-cleavable linkers shift the challenge to correctly identifying the payload release form to measure.
- Free payload sensitivity: this analyte is critical for safety and target release assessment, and often demands ultra-sensitive methods, sometimes to picogram-per-millilitre levels.
“The bioanalysis of ADCs is far more multi-dimensional than that of small molecules and peptides. It requires an integrated and tailored approach to get it right.”
ADCs, PDCs, and AOCs: Same Principle, Different Challenges
Resolian has experience across all three major conjugate modalities, and Andy draws useful distinctions between them.
PDCs (peptide-drug conjugates) use peptides as carriers and are typically analysed by LC-MS. Their smaller size improves cellular permeability, but comes with trade-offs in specificity and stability. Biological sample stabilisation is frequently required.
AOCs (antibody-oligonucleotide conjugates) are a newer class, functioning similarly to ADCs in targeted delivery but carrying therapeutic oligonucleotides rather than highly toxic payloads. This extends the range of treatable targets beyond traditional oligo therapy, but the inclusion of oligonucleotides introduces additional analytical complexity. Hybridisation-based assays and ion-pair chromatography are often needed.
The knowledge built across all three modalities is not siloed. Scientists working on AOCs bring understanding of antibody behaviour from ADC work; those working on PDCs carry technique-level insights from LC-MS-heavy workflows. This breadth is part of how Resolian stays adaptable as the field shifts.
Navigating a Multi-Domain Conjugate Bioanalysis Challenge?
Resolian’s team develops integrated, tailored bioanalytical strategies across ADCs, PDCs, and AOCs, built to scale from preclinical through clinical without rework.
Building for Scalability from Day One
A common failure mode in bioanalytical development is building methods that work in preclinical phase but create friction or rework when transitioning to clinical. Andy describes two specific strategies Resolian uses to prevent this.
Laboratory automation. Reducing manual handling variation is both a reproducibility gain and a scale-up enabler. Automation is implemented not just for efficiency but to reduce the variability risk that comes with high-throughput clinical sample processing.
Early adoption of anti-idiotype antibodies. Generic reagents can save time in early-stage development, but Andy explains that Resolian prefers using anti-idiotype antibodies even at preclinical stages. The experience and knowledge built around those specific reagents can then be carried directly into clinical method development, minimising rework and risk.
Both strategies reflect the same underlying principle: design for the eventual clinical destination, not just for the immediate experiment.
Keeping Pace with Next-Generation ADC Design
Novel linker technologies and site-specific conjugation are reshaping ADC design. Both offer real advantages in therapeutic performance, but they create new analytical problems.
Andy shares a specific example: an ADC with a linker designed to release its payload only in the presence of a particular non-toxic compound via click chemistry. The complication: that releasing compound is stable in vitro, but can be reduced to an inactive metabolite in vivo and then slowly re-oxidised back to its active form, triggering payload release from the ADC unexpectedly.
Resolian conducted a detailed investigation into this releasing chemistry, then refined the approach to eliminate its impact on measurements. It is the kind of problem that could not have been solved by applying a standard protocol. Understanding the mechanism was the prerequisite for designing the assay correctly.
Site-specific conjugation adds a parallel challenge: payloads attached to defined antibody sites rather than random lysine or cysteine residues create more uniform and predictable products, but those products demand more selective and sensitive assays.
“At Resolian, we do not simply adopt previous strategies for novel constructs. We apply the underlying principles behind them.”
Building the Science Team for What Comes Next
When Andy is asked about his philosophy for developing scientific expertise within the team, his answer is direct: the complexity of the work itself drives skill development. Resolian does not need to manufacture challenge, because the modalities they work on provide it naturally.
The breadth of exposure across ADCs, PDCs, and AOCs means scientists build transferable knowledge. They are not just proficient in a single protocol; they understand the underlying principles well enough to adapt when new constructs arrive.
That readiness for what comes next is, in Andy’s view, the defining characteristic of a team that can genuinely keep pace with innovation in this space.
Watch the interview: Watch the full interview on Bioanalysis Zone
Ready to Build Your ADC Bioanalysis Strategy?
Resolian partners with pharma and biotech companies to develop robust, scalable bioanalytical methods for ADCs, PDCs, AOCs, and other complex conjugate modalities.
