Small molecule screening is rapidly evolving to meet the needs of drug discovery. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains the gold standard for analyzing complex samples. Yet, labs face challenges such as low-level analytes, limited resources, data overload and pressure to increase throughput without compromising quality. As drug discovery expands into diverse chemical spaces with AI-driven design, researchers must handle complex samples with higher throughput and reproducibility. Fragmented, manual processes hinder progress and innovation.

The life sciences companies of Danaher are redefining small molecule screening with an integrated approach that transforms fragmented MS workflows into scalable, high-throughput approaches, empowering data-driven decisions in a competitive pharma landscape.

Key challenges and solutions in small molecule screening

• Characterizing complex molecules

  Hybrid modalities and structurally diverse libraries create separation and identification challenges, particularly with PROTACs, degradants and isomers. Traditional LC-MS workflows often involve multiple decision points, which can lead to data silos. Genedata can serve as a central data backbone that integrates with all instruments in a workflow to collect and analyze data, helping to automatically characterize complex molecules. SCIEX’s high-resolution and triple-quad mass spectrometer, paired with Phenomenex’s LC columns, provides deeper structural insights in a single workflow. SCIEX offers untargeted broad-scope high-resolution mass spec (HRMS) screening and targeted quantitative multiple reaction monitoring (MRM), enabling quick characterization. At the same time, Phenomenex’s reverse-phase technology improves the resolution of isomeric compounds. This integrated LC-MS approach reduces multiple assay fragmentation, speeding up the path from detection to structural insights.

• Ensuring reproducibility across labs

  Labs develop custom workflows and methods tailored to their specific small molecule compounds. However, these workflows do not always transfer smoothly between instruments or across sites easily, which can decrease reproducibility and restrict scalability. Often, this causes delays due to revalidations and method setup. Phenomenex’s sample preparation and column chemistries (Luna Omega HPLC/UHPLC LC columns, Kinetex core-shell columns) offer shorter chromatographic gradients with preserved resolution and improved isomer/isobar handling, eliminating the need for complex MS methods. Complementing this, Genedata software can ensure non-biased data analysis. Together, these products are designed to deliver consistent performance across batches and locations, ensuring reliable and reproducible results.

• Pressure for speed without sacrificing quality

  Screening campaigns require faster cycle times; however, increased speed can affect sensitivity, selectivity or long-term robustness. SCIEX platforms support both high throughput and detailed analysis, from ultrafast LC-MS screening to comprehensive HRMS and DIA/SWATH techniques. Genedata is designed for handling high-throughput processes and can quickly analyze data, saving significant amounts of time in these workflows. This approach provides a robust and reproducible assay solution without compromising quality.

A new vision for integrated screening

Integrated workflows enable discovery teams to focus on advancing molecules, scaling from hundreds to tens of thousands of compounds by integrating SCIEX’s precision and Phenomenex’s innovations in sample preparation and chromatographic selectivity. Coupled with Genedata’s advanced analytical and integrated data management approaches, this enables the capture of high volumes of data and the automation of workflows. This integration characterizes complex small molecules with fewer assays, ensuring reproducibility and actionable data across the discovery pipeline. These screening platforms even support emerging modalities without constant reworking, allowing accelerated decision-making and enabling earlier resource allocation.

SCIEX, Phenomenex and Genedata solutions enable high-throughput primary screening, such as plate-based enzyme or transporter assays, to process large sample numbers. For secondary screens, such as quantitation panels, DMPK profiling and metabolite detection, labs can achieve sub-ng/mL quantitation with reliable retention and minimal reprocessing. Genedata’s analysis software provides automation, accuracy and collaboration to streamline reporting without the need to rerun plates. Genedata delivers efficient screening of degradants, off-targets or unexpected matrix components.

The future of small molecule screening will be led by organizations that address the issues of scalability and reproducibility. Learn how the life sciences companies of Danaher can help your lab transition from disjointed, inefficient assays to comprehensive, harmonized solutions that speed up discovery.