High-Throughput Mass Spectrometry for Hit Identification: Current Landscape and Future Perspectives

Area of Science:

• Biochemistry
• Analytical Chemistry
• Pharmacology

Background:

• Mass spectrometry (MS) has been a valuable tool in drug discovery for nearly 20 years.
• It serves as a label-free, direct-detection method for screening therapeutic targets.
• MS is applicable to both functional and affinity-based screening assays.

Purpose of the Study:

• To provide an overview of established and emerging mass spectrometry platforms for high-throughput screening (HTS).
• To summarize the unique strengths and performance characteristics of different MS techniques in drug discovery.
• To illustrate the power of MS in identifying drug leads through literature examples.

Main Methods:

• Review of existing literature on mass spectrometry applications in HTS.
• Analysis of established and emerging MS platforms.
• Case study examples showcasing MS differentiating power compared to other detection methods.

Main Results:

• Mass spectrometry platforms offer sensitivity, specificity, wide dynamic range, and complex matrix compatibility.
• MS enhances the discriminating power and physiological relevance of screening assays.
• Examples demonstrate MS's effectiveness in identifying hits, leads, and potential drugs.

Conclusions:

• Mass spectrometry is a powerful and versatile technique for drug discovery screening.
• Its inherent strengths enable enhanced identification of therapeutic candidates.
• This review serves as a guide to the applicability and benefits of MS in drug development.