Pharmaceutical and agrochemical companies discover new
products by high throughput screening (HTS) of large
numbers of compounds against biological targets.
Typically, when 10,000 compounds are screened, a lead
compound is discovered and then, by following such leads,
one new product is eventually developed. Companies acquire
and store hundreds of thousands of compounds for this
process. Some of these compounds (conservative estimate:
ten percent) are unstable and decompose during storage.
Causes of this decomposition are handling (e.g. the
solvents used)and storage conditions (thermal, hydrolytic
No-one knows for sure how serious this problem is but
everyone acknowledges that it does cost money because
of the misleading HTS results from decomposed compounds.
This project will examine the stability of compounds stored
by companies using their own in-house analytical data.
Several European pharmaceutical and agrochemical companies
will provide their data for this study. At the same time,
other sets of compounds will be selected at random and
subjected to accelerated decomposition conditions (thermal,
hydrolytic and oxidative) and analysed at regular
intervals. The combined results will identify compound
types which are likely to decompose during storage.
On the basis of the results it is possible to protect
compounds during storage but, to mitigate costs, the
protective environment should be limited to only those
compounds which really need it.
Furthermore, predictive software which connects compound
structure to observed instability will be developed.
Companies will be able to use this software to predict the
(in)stability of compounds and the causes.
Keywords: compound decomposition.