omation mbers - Society for Laboratory Automation and Screening

10:30 am Thursday, February 5 High Throughput Screening — ADME – Tox Room A2
Arun Mandagere
Pfizer Global Research and Development
006/460, 2800 Plymouth Road
Ann Arbor, Michigan 48105
arun.mandagere@pfizer.com
Role of Automated High Throughout Nephelometric Aqueous Solubility System in
Early Drug Discovery
We describe an automated high throughput Nephelometric aqueous solubility system that has played a critical
role in the successful selection of quality lead candidates in early Drug Discovery programs. Aqueous solubility is
used to gauge dissolution, adsorption and bioavailability of lead compounds. The advantage of a Nephelometric
solubility screen is its ability to measure solubility at a comparable rate to secondary HTS pharmacological screens
with minimal sample requirement. This process enables in the rapid identification of poorly soluble compounds
with good activity, which are very likely to fail due to poor adsorption or low bioavailability. More importantly, this
process provides timely feedback to medicinal chemist to pursue synthetic strategies in the producing compounds
with good activity and solubility. Unlike the classical thermodynamic solubility measurements, the Nephelometric
HTS solubility system is uniquely suited for early drug discovery because its speed, high capacity and small
sample requirement. We will highlight the system components, assay parameters, and automated data analysis
software used in building this automated solubility screening system. The Nephelometric HTS Solubility System
increased sample throughput from 100 to 1800 compounds per week, and a 75% reduction in compound usage
when compared to the HPLC- based flow-injection analysis (FIA) solubility method. The results generated by the
HTS Nephelometric solubility method show a good agreement with those of HPLC-FIA solubility method.
11:00 am Thursday, February 5 High Throughput Screening — ADME – Tox Room A2
Ken Matuszak
Abbott Laboratories
100 Abbott Park Road
Abbott Park, Illinois 60064-6122
ken.matuszak@abbott.com
Higher Throughput Strategies for Support of Early ADME In-vitro Screening
What is “high throughput”? In many ways, for an analytical chemist, this is equivalent to the question of what is
“zero.” For some applications (such as the structural elucidation of a completely unknown chemical entity), high
throughput could mean just one complete analysis per day. For others (such as an assay for a specific drug in
plasma samples from clinical studies) it might mean thousands of samples analyzed, quantitated, and reported
in a 24-hour period. This presentation will focus on practical techniques for increasing throughput (“higher
throughput”) for the analytical support of in vitro ADME screens (plasma protein binding, metabolic stability, and
permeability) that are used in the support of Discovery research. While a few corporations have fully automated
this type of work, and have already optimized their sample analysis throughput, many companies continue to use
more traditional tried and true methods. These methods, while robust and reproducible, are far from optimized
for maximum throughput. Methods discussed will include high throughput universal gradients coupled with mass
spectrometric (MS) analysis, parallel solid phase extraction (SPE) and sequential elution to an MS, and quadrupoletime
of flight MS vs. triple quadrupole MS.
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PODIUM ABSTRACTS