Bioanalysis最新文献

Blood sampling and diagnostic laboratory analysis are important aspects of our healthcare systems and patient management. However, the process by which the majority of blood specimens are currently collected, venipuncture, does not put the needs of the patient at the center of the process. This article explores the potential utilization of patient centric sampling (PCS) for the collection of smaller blood volumes using technologies that can enable this sampling to take place at a time and location that is more comfortable and convenient for the patient, including self-sampling at home. We discuss the benefits of these technologies, where they are currently used (including case studies), what to consider when contemplating their use and the current regulatory environment. We then explore why the routine adoption of these technologies has been relatively slow and how this impasse may be overcome for the benefit of all patients. This article describes a viable alternative approach for the collection of diagnostic specimens that puts the requirements of the patient at the center. It provides an invaluable resource for those interested in learning about and potentially implementing this approach into their workflows and addresses the concerns that individuals and organizations may have when doing so.

Tumor-associated genetic markers are useful for early cancer screening, diagnosis, and treatment monitoring. However, traditional detection methods are complex in operation procedures, time-consuming, and the equipment costs are expensive. CRISPR/Cas systems are becoming emerging detection tools for tumor detection due to their programmability, rapid reaction, high targeting specificity, and the ability to amplify the signals. CRISPR/Cas has made breakthroughs in the detection of tumor-associated genetic materials including gene mutations, DNA methylation, miRNA, lncRNA, and circRNA detection. Herein, we critically discuss these advancements and describe the key concepts of each CRISPR/Cas system for detecting tumor-associated genetic materials. The significance of these tumor-associated genetic materials in cancer diagnosis and prognosis is highlighted.

Aim: To improve the integrity and comparability of pharmacokinetic data in clinical trials by refining the statistical assessment methodology for cross validation of bioanalytical methods across multiple laboratories.

Materials and methods: Cross validation assessments were conducted using statistical tools recommended by International Council for Harmonization M10 guidance, including Bland-Altman plots, Deming regression, and Lin's Concordance. Recognizing limitations in Deming regression and Lin's Concordance for interpreting cross validation results, we introduced a combined approach: Bland-Altman plots with equivalence testing. The acceptance threshold was defined such that the 95% confidence interval of the mean log10 difference between laboratories must fall within boundaries based on method validation criteria.

Results: The proposed methodology was validated across diverse bioanalytical methods. Unlike conventional approaches that impose strict constraints on Deming regression parameters, our framework accommodates practical assay variability. This approach provided consistent and credible cross validation outcomes in real-world scenarios.

Conclusions: Integrating Bland-Altman plots with equivalence boundaries offers a robust, statistically sound framework for cross validation in bioanalytical studies. This method enhances the quality and consistency of pharmacokinetic data, supporting more reliable clinical trial endpoints.

Xylazine is a veterinary sedative that is frequently detected in the illicit drug supply, often found mixed with illicitly manufactured fentanyl (IMF). It has been detected in the blood of overdose victims and patients who use illicit drugs. Xylazine is not approved for use in humans. It is an alpha-2-adrenergic receptor agonist that causes deep sedation that is non-responsive to naloxone, the antidote for opioid overdose. Chronic exposure to xylazine has been linked to severe wounds that can progress to amputation. Medetomidine is another related veterinary sedative that has more recently emerged as an adulterant in IMF. Medetomidine is also an alpha-2-adrenergic agonist, and in veterinary medicine it is known to be significantly more potent than xylazine. The mixture of these drugs with IMF complicates the treatment of patients exposed to these drugs. Wider availability of analytical methods to detect xylazine, and now medetomidine, is crucial for responding to these health threats and increasing knowledge on the harms and potential therapies for exposed patients. This review covers what is currently known about these drugs, including observed concentrations in various biospecimens, expected major metabolites and windows of detection, and available analytical approaches for detecting exposure.

Only a small fraction of disease-modifying proteins present druggable pockets for conventional small-molecule or biologic therapies, underscoring the urgent need for innovative strategies such as nucleic acid-based antisense therapeutics. Antisense approaches-including antisense oligonucleotides (ASOs), RNA interference (RNAi), and decoy oligodeoxynucleotides (ODNs)-offer powerful means to directly modulate gene expression at the RNA level. Over the past four decades, these modalities have advanced from early proof-of-concept studies to numerous FDA- and EMA-approved therapies for neuromuscular, metabolic, and neurodegenerative diseases. Despite these successes, critical barriers remain. Antisense drugs face challenges related to nuclease degradation, off-target binding, dose-dependent toxicities, limited tissue penetration, and inefficient endosomal escape. Addressing these limitations will require advances in nucleotide chemistry, conjugation strategies, and delivery platforms. Personalized "N-of-1" therapies further highlight the promise of customized oligonucleotides but also raise ethical and cost considerations. This review synthesizes the current state of antisense modalities, the obstacles impeding their broader application, and the innovative approaches needed to upgrade existing platforms and expand their therapeutic potential across a wider range of genetic and acquired diseases.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use M10 guideline provides a global framework for bioanalytical method validation in studies intended for regulatory submission. While its structure ensures consistency and data reliability, the guideline also acknowledges that not all studies require the same level of validation. This paper examines where full compliance is essential and where scientific judgment allows for leaner, context-driven validation, such as in early-stage development, for additional matrices, metabolites, nonstandard biological matrices or studies intended for internal decision-making. Drawing on recent recommendations from the European Bioanalysis Forum, we introduce a decision-making flowchart and parameter table to support consistent application of a Context-of-Use approach to validation. These tools help guide when flexibility is appropriate while ensuring transparency and robustness in the data. The paper advocates continued dialogue both with end users of the data and the regulatory authorities to support a modernized, risk-based validation framework that remains aligned with patient needs and scientific integrity. We believe the recommendations in this paper are fully in alignment with the intent and core principles of ICH M10, while encouraging their application in a way that remains scientifically driven and proportionate to the purpose of the assay.