Catch up on the most read articles from 2025
We’re back with a new journal reading list, this time with the top six most read articles from Bioanalysis in 2025!
Explore updated European Bioanalysis Forum recommendations, a commentary on FDA biomarker validation gaps, and the rising public health threat of xylazine and medetomidine in illicit drug supplies.
A question to mull over while you read: Where do you side in these impactful discussions?
Whole blood stability in bioanalytical method validation: updated recommendations from the European Bioanalysis Forum
Whole blood stability testing is critical to ensuring that analyte concentrations remain consistent from collection to analysis, as emphasized by both US FDA and EMA guidelines. The updated recommendations address key considerations such as the definition of fresh blood, equilibration times, assay types, and the timing of testing during method development and validation. These updates incorporate evolving practices since the EBF’s initial 2011 recommendations, aligning with the ICH M10 guidelines and emphasizing adherence to the 3Rs principles to refine and improve testing methodologies.
Development of an LC–MS/MS assay to analyze a lipid-conjugated siRNA by solid phase extraction (SPE) in mouse plasma and tissue using a stable isotope labeled internal standard (SILIS)
Researchers developed and optimized a solid-phase extraction (SPE) method combined with LC–MS analysis to quantify lipid-conjugated siRNA molecules, which are challenging to analyze due to their increased hydrophobicity from fatty acid conjugation. Using a stable isotope labeled internal standard (SILIS), they achieved high accuracy and precision (±5%) in measuring these therapeutics in mouse plasma and tissues, demonstrating that this approach could become standard practice for siRNA bioanalysis.
Comparing capillary blood collection technologies: assessing patient experience, device performance, & clinical accuracy
This paper evaluates and compares five capillary blood collection technologies (CCTs), including four upper arm methods and a traditional fingerstick, against venipuncture in a cross-sectional study involving 41 healthy participants. The study assesses user experience (e.g., pain, preference), collection performance (e.g., sample volume, quality, and time), and clinical accuracy relative to venipuncture results, as well as post-collection healing. While no single technology emerged as superior, all demonstrated comparable clinical accuracy, suggesting that the choice of technology may depend on the target population and specific use cases. The findings highlight the potential of CCTs to enhance patient-centric healthcare by offering less invasive, more accessible blood collection methods, though further advancements and studies are needed to ensure analyte equivalency with venous specimens.
Read the full Research Article
Special consideration: commentary on the 2025 FDA Bioanalytical Method Validation for Biomarkers
The FDA’s new 2025 Bioanalytical Method Validation for Biomarkers (BMVB) guidance creates a regulatory gap by directing biomarker assay validation to use ICH M10 as a starting point, despite ICH M10 explicitly excluding biomarkers from its scope, leaving no clear guidance for appropriate biomarker validation that supports context-of-use requirements. The authors advocate for using the 2019 Critical Path Institute’s Points to Consider document, which was developed with FDA input and provides a fit-for-purpose framework based on context-of-use principles, as the most appropriate current resource for biomarker assay validation until more comprehensive guidance is developed.
European Bioanalysis Forum recommendation on embracing a context-of-use-driven scientific validation for chromatographic assays in the light of ICH M10
The ICH M10 guideline establishes a global framework for bioanalytical method validation in regulatory studies, but recognizes that not all studies require the same validation rigor, allowing for scientific judgment in applying leaner, context-driven approaches for early-stage development or internal decision-making studies. This paper presents a decision-making flowchart and parameter table based on European Bioanalysis Forum recommendations to guide the appropriate application of a context-of-use validation approach, advocating for continued dialogue with regulators to support a modernized, risk-based framework that maintains scientific integrity while being proportionate to the assay’s intended purpose.
Recent advances in the identification and quantification of xylazine and medetomidine in biological specimens
This Review highlights the growing prevalence of xylazine and medetomidine, veterinary sedatives not approved for human use, as adulterants in illicitly manufactured fentanyl (IMF), posing significant public health risks. Xylazine, first detected in drug supplies in Puerto Rico and Philadelphia, has been increasingly linked to overdose deaths and severe skin ulcerations, while medetomidine, a more potent alpha-2 adrenergic agonist, has emerged more recently, with cases of overdose reported in Chicago. Both drugs complicate treatment as their effects are non-responsive to naloxone, the opioid antidote, and their addition to IMF may enhance euphoric effects while causing profound sedation, cardiovascular depression and other adverse effects. The Review emphasizes the urgent need for reliable analytical methods to detect these substances and their metabolites in biological specimens to support clinical management, forensic investigations, and public health monitoring.
More journal-related content:
