Designing fit‑for‑purpose LC–MS biomarker assays: a sneak preview from Shane Karnik
In anticipation of Aliri Bioanalysis’s (CO, USA) webinar, we spoke with Shane Karnik about his WRIB activities, as well as what to look forward to in the upcoming talk with Bioanalytical Scientist Niki Gonzales.
Shane Karnik
Sr. Laboratory Director
Aliri Bioanalysis
Shane Karnik joined Aliri Bioanalysis in 2003 and currently serves as Senior Laboratory Director. In this role, he leads a team of scientists executing bioanalytical programs that support pharmaceutical drug development across both non-GLP and regulated (GLP/GCP) preclinical and clinical studies. His work spans a wide range of analytical platforms, including nominal and high-resolution mass spectrometry, advanced chromatographic techniques, and automated sample preparation systems. Shane has extensive experience in the extraction and quantitation of small molecule drugs, therapeutic peptides, biologics and oligonucleotide-based therapeutics. In addition to his scientific leadership, he plays a key role in ensuring technical rigor and regulatory compliance across all projects at Aliri. Prior to joining Aliri, Shane Karnik earned a Master of Science in Chemistry from the University of Colorado (CO, USA) in 2000 while working full-time in research and development at a medical device company. He remains actively engaged in the scientific community as a member of the Bioanalytical CRO Council, contributor to AAPS bioanalytical focus groups, and member of the American Society for Mass Spectrometry.
1. Your poster at WRIB 2026 focused on optimizing surrogate matrix selection for endogenous biomarker LC–MS assays. Can you talk us through the main takeaways of the poster?
The poster focused on the need to move beyond simple surrogate matrices and instead engineer surrogate matrices that are physiologically closer to the authentic matrix. Rather than relying on generic substitutes, the Aliri team explored approaches to selectively remove the components responsible for endogenous interference while maintaining overall matrix relevance.
A key theme was achieving protein balance equivalence between the surrogate and authentic matrix. We also evaluated targeted removal of specific components from the authentic matrix to better understand how to rationally design engineered surrogate systems that more closely align with real biological conditions, ultimately improving assay performance and the ability to control or normalize matrix effects in LC–MS analysis.
2. At this year’s bioanalytical events so far, what has been the general discourse around deploying LC–MS-based biomarker assays?
At this year’s bioanalytical events, there has been growing discussion around hybrid LC–MS workflows that use immunoprecipitation as a sample enrichment step prior to LC–MS analysis. These methods are viewed as a bridge between traditional ligand-binding assays (LBAs) and direct digestion LC–MS approaches. Key advantages include improved selectivity and sensitivity, reduced matrix interference, and higher molecular specificity compared to LBAs. A practical benefit is the ability to use commercially available or even less selective antibodies for enrichment. However, challenges remain, including increased method complexity, variability in the immunocapture step, higher reagent and development costs, and longer turnaround times versus standard LBAs.
3. Looking ahead to your upcoming webinar, can you share a sneak peek of what attendees can expect?
We will be talking about how to clearly define the “context of use” for LC–MS-based biomarker assays and how that drives the right level of assay qualification. We’ll also share some real-world data that Aliri Bioanalysis has generated on surrogate matrix selection to help normalize performance between incurred samples and surrogate calibrators, along with how endogenous QCs can be used to track assay performance over time and throughout a study.
4. Who would you encourage to attend the session?
I’d encourage anyone working in bioanalytical development — especially those involved in LC–MS-based biomarker or PK/PD assay development — to attend. That includes scientists and study leads thinking about assay strategy, qualification or validation, as well as those deciding between LBA and LC–MS approaches.
Find our collection of webinars here.
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Bioanalysis Zone or Taylor & Francis Group.
