New instruments can help streamline the drug discovery process
and improve its cost effectiveness.
With drug development cost estimates exceeding $1 billion per drug and an increasing failure rate for lead drug candidates in the development process, the pharmaceutical industry is focused on ways to improve output and efficiency. New analytical instruments and methods are one way to increase productivity and cost effectiveness of the entire drug discovery and development process.
Rolling out new platforms
The drug discovery and development process is being aided by new analytical instruments and methods.
Applied Biosystems, Foster City, Calif., and SCIEX, San Francisco, Calif., a division of MDS Inc.’s Analytical Technology business, are developing FlashQuant, a mass spectroscopy platform designed to help pharmaceutical companies accelerate the drug compound screening process. The FlashQuant platform will combine triple quadrupole mass spectrometry with MALDI technology. Laboratory tests conducted by Applied Biosystems/MDS SCIEX with the new platform have consistently delivered a 25-fold increase in speed for small molecule quantitation, compared with the fastest liquid chromatography-coupled triple quadrupole mass spectrometers currently in the market.
“Pharmaceutical scientists are looking to deliver quality information faster and with more consistent results,” says Laura Lauman, president of Applied Biosystems’ proteomics and small molecules division.
“We believe that the FlashQuant system will improve early drug discovery by increasing the speed and number of compounds that can be profiled. This could potentially result in more efficiency and greater ROI in the drug development process, by enabling important development decisions to be made earlier and with more reliability.”
One of the initial applications expected for the FlashQuant platform is early absorption, distribution, metabolism, and excretion (ADME) profiling in pharmaceutical discovery laboratories, a key step in the screening of candidate compounds. Mark Cole, a research fellow at Pfizer Pharmaceuticals, Groton, Conn., oversees an ADME laboratory that runs an average of 75,000 samples per five-day week to provide ADME data to early discovery projects. The data his laboratory generates is funneled back to chemists who use it to optimize the ADME properties to provide better compounds for development. “The tremendous increase in speed unlocks a lot of potential for our lab, allowing us to consider running experiments that we don’t have capacity for now,” says Cole. “With this throughput, we could essentially ‘front-load’ discovery, which increases the chances of ultimately getting a compound to market.”
Aiding high-throughput screening
PerkinElmer, Inc., Waltham, Mass., has launched its new 1536 Head LumiLux Cellular Screening Platform for high-throughput screening (HTS) and ultra high-throughput screening (uHTS) kinetic flash and glow luminescent cellular assays.
With advanced liquid handling automation for walk-away capability, the 1536 LumiLux Cellular Screening Platform is the only dedicated flash luminescence instrument that enables simultaneous 1536 “inject and read” flash luminescence assays, allowing laboratories to produce over 100,000 data points per day.
Flash luminescence platforms are increasingly utilized by pharmaceutical companies over traditional fluorescence technologies for primary and secondary screening of drug targets. According to recent market research, 50% of HTS labs are expected to switch from the traditional kinetic fluorescence assays to flash luminescence technologies in the next two to three years.
“Flash luminescence provides a highly sensitive tool for assaying the very important GPCR target class without the artifacts or false positives normally associated with fluorescent detection, providing more physiologically relevant data,” says Mary Duseau, business leader, Detection and Analysis Systems, Molecular Medicine Business Element for PerkinElmer Life and Analytical Sciences. “The 1536 miniaturized format and ‘inject and read’ automation capability significantly ramps up the throughput to meet the rigorous performance requirements of the most demanding labs, dramatically increasing productivity and improving cost-efficiencies.”
“The 1536 tip LumiLux Screening Platform will allow Kalypsys to significantly increase the throughput of flash luminescent GPCR screens,” says Rob Bukar, associate director of screening, Kalypsys, Inc., San Diego, Calif., an innovative clinical stage pharmaceutical company which recently adopted the LumiLux platform for its uHTS screening labs. “Increased throughput reduces the time it takes to complete a screen and often results in greater consistency when comparing data across a large number of plates. Since the 1536 LumiLux was designed to be optimized for the low volume requirements of 1,536 well assays, we expect improved well-to-well variance across the plate and greater accuracy in our results.”
Complete solutions
Thermo Fisher Scientific Inc., Waltham, Mass., showcased its latest LC-MS/MS quantitation solutions designed for drug discovery and development applications at Pittcon in Chicago, Ill., earlier this year. Their solutions incorporate the Thermo Scientific TLX high-speed liquid chromatography (LC) system with TurboFlow technology, the TSQ Quantum series triple quadrupole mass spectrometers, high-field asymmetric waveform ion mobility spectrometry (FAIMS) technology, the Accela high-speed chromatography system, and Watson LIMS.
TurboFlow technology provides high sensitivity through reduced ion suppression and matrix effects. It works by retaining small molecules and filtering out proteins and larger materials by diffusion, size exclusion, and column chemistry. This enables users to directly inject biological samples into the MS/MS system for analysis and creates a significant advantage in preclinical bioanalysis, where extensive sample preparation is very time-consuming due to high sample loads.
The TSQ Quantum series triple quadrupole mass spectrometers incorporate highly-selective reaction monitoring (H-SRM) performance technology, allowing users to analyze complex samples quickly and efficiently. The combination of the TSQ Quantum and H-SRM provides researchers with a toolkit to address the challenges of developing highly specific and highly sensitive LC-MS/MS methods for drug quantitation.
FAIMS technology significantly enhances assay robustness and sensitivity by eliminating drug-related, endogenous, and nonendogenous chemical interferences. The FAIMS device is installed in the atmospheric pressure region between the ion source and the mass spectrometer, enabling three complementary dimensions of separation: LC, FAIMS, and H-SRM.
The software incorporated in the Thermo Scientific LC-MS/MS quantitation solutions addresses the complete process of drug discovery and development. During the drug discovery phase, a TSQ Quantum powered by QuickQuan software provides workflow automation that significantly improves the throughput of drug discovery assays. During DMPK/Bioanalytical studies in the drug development phase, Watson LIMS and LCquan software provide a seamlessly integrated solution that facilitates confident data submission for regulatory purposes.
