The expanding role of LC–MS in support of small molecule drug development programs

As sponsors increasingly bring forward complex drug development strategies, the bioanalytical scientists must keep up with delivering validated assays to answer key questions about safety and efficacy. For example, to enhance small molecule drug pharmacology and exposure at the site of interest, small molecules are often conjugated (e.g., to an antibody, protein, or biodegradable polymer) and/or encapsulated (e.g., liposomes, micelles, or lipid nanoparticles) to protect and target the drug delivery to the site of interest.

Appropriately, bioanalytical assays are required to monitor both the small molecule and the delivery/conjugated moiety. Similarly, new gene therapies increasingly include a combination of oligonucleotide strands intended to address multiple points of genetic deficiencies, delivered in nanoparticle format. New benchtop HRMS mass spectrometers, such as the Thermo Exploris, are finding advantages over triple quadrupole MS for increased selectivity and assay development speed. Lastly, requirements for demonstrating drug safety necessitate complex biomarker assays that may be constrained by sensitivity, stability and limited sample volume. We will profile a highly sensitive assay for monitoring thyroid hormones T3 and T4 in gestational rat pups using only 20 µL of rat pup serum, including sharing the statistical power of the methods with study data.

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