by Roger Hayes, PhD
As promising drugs emerge with high-potency, active ingredients, new technological tools to analyze them are emerging.
In my previous blog , I covered some of the unique challenges that these drugs pose to bioanalytical testing. Most of those issues involve eliciting reliable, high-quality data from ever-shrinking sample volumes.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains an important method in bioanalytical testing tools. Among the most significant contributions to improving LC-MS/MS is the development of chromatography columns packed with sub-2m stationary phase particles. When analyzing volume-limited drug samples, these smaller particles offer higher peak efficiencies, improved resolution and, ultimately, higher throughput assays.
Along this line, fused-core silica particle technologies afford another approach for high- throughput LC-MS/MS assays. This technology relies on a solid particle surrounded by a porous silica layer to reduce the impact of mass transfer, thereby generating greater efficiency.
Of course, being faster and more efficient is just part of the equation. We also need technologies that are more sensitive, especially when working with minute volumes of highly potent drugs. Some investigators have turned to accelerator mass spectrometry. AMS accelerates ions to several percent of the speed of light, generating high kinetic energies and allowing better mass selectivity and specificity. The result is sensitivity up to 1,000 times better than conventional LC-MS/MS.
Then there are the latest ligand-binding assays. These rely on electrochemiluminescence and fluorescence, using optical signals and light detectors that both broaden the dynamic range of an assay and increase sensitivity. Also, there are ultra-sensitive platforms and label-free ELISAs (enzyme-linked immunoabsorbent assays) that greatly advance the science. For example, the immune-polymerase chain reaction system that links standard immunoassays with immense signal amplification has enhanced sensitivity as much as 10,000-fold.
Beyond more precise and sensitive assay tools is the evolution of predictive models. Typically, researchers correlate in vivo plasma concentration versus time and toxicity curves to in vitro concentration versus toxicity response curves across many compounds, then they determine the mathematical relationship between both sets of data. Unfortunately, this process doesn’t always yield accurate and meaningful results.
That’s why there is an industry collaboration in place to tackle this issue. Called the Predictive Safety Testing Consortium, it brings together pharmaceutical companies and the U.S. Food and Drug Administration to identify toxicity biomarkers that can be translated between animal models and human patients.
Clearly, the pace of change in drug development will continue to drive the evolution of bioanalytical testing. As a scientist, it’s exciting for me to participate on the cutting edge of this essential scientific enterprise.
Roger Hayes, PhD, is Vice President and General Manager of Laboratory Sciences at MPI Research. For more on high-quality, cost-effective bioanalytical testing, contact us at firstname.lastname@example.org.