Optimizing Surrogate Matrix Selection for Endogenous Biomarker LC-MS/MS Quantitation Assays
Historically, LC-MS/MS focused on synthetic drug pharmacokinetics. However, improved sensitivity now allows the analysis of endogenous biomarkers (lipids, proteins, etc.) previously reserved for Ligand Binding Assays (LBA). A primary challenge in biomarker bioanalysis is that these compounds are endogenous to biological matrices, and the matrix could present challenging physicochemical properties. Unlike conventional drug testing, there is no true blank matrix available to build calibration standards. To quantify these levels accurately, researchers must develop a surrogate matrix that mimics the behavior of authentic patient samples without the background interference of the natural analyte. Selecting and validating this surrogate is the most critical step in establishing a reliable LC-MS/MS method for any naturally occurring compound.
Download our poster, recently presented at WRIB 2026 to learn more.
Advanced Bioanalytical Support for Oligonucleotides
Aliri has supported 5 of the 20 approved OGNs on market as they transitioned from preclinical to clinical to FDA approval Aliri is proud to be a trailblazer in the bioanalysis of RNAi therapeutics with significant experience supporting the development of oligonucleotides, which includes siRNAs, ASOs, PPMOs, ARCs/AOCs, and other RNAi conjugates.
Our tenured team of scientists are continuously innovating and adapting our methodologies for improved
assay sensitivity and specificity to deliver accurate and reliable data to our sponsors.
This has led to the critical application and optimization of available analytical approaches, including novel SPE and hybridization extraction techniques that can achieve subnanogram per milliter LLOQ’s with the
specificity of LC/MS detection.
Download the fact sheet to learn more.
The Complexity of the Gastrointestinal Tract: A Multilayered Challenge for Drug and Biomarker Studies
The gastrointestinal (GI) tract is a highly specialized and dynamic system, playing a central role in digestion, absorption, immune response, and microbiome interaction. From the stomach to the small intestine (duodenum, jejunum, ileum) and the large intestine (colon, rectum), each segment presents unique physiological and structural characteristics that influence drug delivery and disease progression.
Aliri’s spatial imaging capabilities allows you to understand drug behavior and biomarker expression across the four main layers of the intestinal wall.
Download the fact sheet to learn more.
Oligonucleotide Hybridization LCMS Workflows and Probe Optimization
In this scientific poster recently presented at EBF Open Symposium, we investigated the biodistribution and potential toxicity of lipid nanoparticles (LNP1 and LPN2), which are crucial carriers for mRNA-based treatments after administration to male and female mice, analyzing their distribution in whole-body carcasses and specific organs using MALDI-MSI.
Download our poster to learn more.
Mapping mRNA–Lipid Nanoparticle Distribution in Mouse Whole Body and Organs by MALDI-MSI
In this scientific poster recently presented at EBF Open Symposium, we investigated the biodistribution and potential toxicity of lipid nanoparticles (LNP1 and LPN2), which are crucial carriers for mRNA-based treatments after administration to male and female mice, analyzing their distribution in whole-body carcasses and specific organs using MALDI-MSI.
Download our poster to learn more.
Ring Trial Study Results for Oligonucleotides Prove Hybridization LC-MS Approach Superior to LBA in Achieving Lower Detection Limits and Higher Specificity
Aliri was recently one of 10 labs to participate in the Oligonucleotide Ring Trial, in which industry experts joined together to evaluate the effectiveness of LC-MS, LBA, and qPCR when quantifying the concentrations of oligonucleotide in biological samples. This first-of-its-kind study aimed to give clarity to drug developers about the methodology best suited for future development programs. Specifically, the Ring Trial focused on three types of oligonucleotides, an ASO (Fomivirsen), a GalNAc-siRNA (Lumasiran), and a PMO (Viltolarsen).
Troy Voelker, Sr. Lab Director at Aliri and Chair of the AAPS Oligonucleotide Discussion Group, led the LC-MS method development of the PMO (Viltolarsen), which was analyzed using three mass spectrometry platforms: a QExactive, a time-of-flight (TOF), and a triple quadrupole instrument. In this presentation, he reveals exciting data that proves hybridization LC-MS superior to LBA in achieving lower detection limits and higher specificity.
Download the presentation to read the study findings.
Enabling Clinical Adoption of Omics: Fit-for-Purpose Validation and a Spatial Biomarker Case Study
Over the past two decades, omics technologies have steadily expanded from discovery research into translational and clinical development, offering unprecedented insights into biology, disease mechanisms, and therapeutic response. Advances in genomics, transcriptomics, proteomics, metabolomics, and, more recently, spatial and multi-omics platforms have created powerful opportunities to identify predictive biomarkers, refine patient stratification, and accelerate drug development. The added value of omics lies in their ability to capture complex, system-level biology that traditional single-analyte assays cannot address, thereby bridging the gap between exploratory research and precision medicine.
Yet this rapid progress has also highlighted a critical challenge: how to validate omics data in a way that is scientifically rigorous but also practical. Current analytical validation paradigms were largely developed for conventional assays such as ELISA or qPCR, which measure one or a handful of targets at a time. Applying the same frameworks directly to high-dimensional omics assays often results in processes that are overly burdensome, expensive, and poorly aligned with the dynamic nature of omics platforms.
Moving forward, the field needs more efficient and adaptive validation processes, aligned with the specific purpose of each omics application. This involves applying full rigor when data will inform regulatory submissions or clinical decisions, while using streamlined, fit-for-purpose approaches for exploratory research and mechanistic studies.
In this presentation, Aliri R&D Director and Spatial-Omics Expert, Corinne Ramos, Ph.D., illustrates these challenges and opportunities through a spatial multi-omics use case, where paired patient biopsies were profiled with spatial transcriptomics and proteomics to uncover mechanistic insights, identify predictive biomarkers, and generate regulatory-ready evidence for clinical development.
Download the presentation to learn more.
Maximizing Reproducibility and Sensitivity in qPCR for Detecting Transcripts Over a Broad Dynamic Range in Response to Anti-PD-1 Therapy
This study aims to optimize and validate a qPCR workflow for the reproducible and sensitive quantification of immune checkpoint transcripts (PD-1,PD-L1, CTLA-4) in FFPE lung cancer tissues. By refining tissue preparation, RNA input, and assay conditions, we establish a robust method for detecting gene expression across a broad dynamic range, enabling reliable assessment of immunotherapy response and supporting biomarker-driven patient stratification.
Download our poster to learn more.
Development and Validation of a Sensitive LC-MS/MS Method for the Quantification of SGR-1505 in Human Plasma to Support Clinical Pharmacokinetic Studies
MALT1 is a key mediator of NF-κB signaling and an emerging therapeutic target in B-cell malignancies and autoimmune diseases. SGR-1505, a potent MALT1 inhibitor, is being clinically evaluated for its therapeutic potential. In this study, we developed and validated a reliable and high-throughput LC-MS/MS method for the quantitation of SGR-1505 in human plasma (K₂EDTA) to support clinical pharmacokinetic studies. This work exemplifies the critical role of CRO-led bioanalysis in bridging early discovery and clinical development of emerging therapeutics.
Download our poster to learn more.
Development of Total ASO method in Mouse Plasma and Tissues Using LC-FD and LC-MS Platforms
Bioanalytical methods are needed to analyze protein conjugated antisense oligonucleotides (POCs) to accurately quantify the active antisense oligonucleotide (ASO) payloads, assess its pharmacokinetics and biodistribution in plasma and tissues, and ensure patient safety by evaluating potential immunogenicity and toxicity. Because the conjugate, the free ASO, and the linked ASO fragment can all be present, specialized techniques are required to differentiate and quantify these components, which is essential for supporting the development of these complex biotherapeutics. The unique properties of POCs present significant analytical challenges that necessitate specialized methods.
We set out to develop a methodology for quantifying total ASO in POCs that could be universally applied across similar POCs. The
study compared mass spectrometry and fluorescence detection platforms to determine optimal sensitivity, selectivity,
and adaptability. Additionally, it aimed to establish a single extraction method suitable for both plasma and tissue
analysis.
Download our poster to learn more.