Published:Journal of Chromatographic Science,
ISSN 0021-9665Volume
40, Number 5, May/June 2002, pp. 292-296
Preparative High-Performance Liquid Chromatography–Mass
Spectrometry for the High-Throughput Purification of Combinatorial Libraries
Marcus Bauser
Medicinal Chemistry VII, Business Group Pharma, BAYER AG, 42096 Wuppertal, Germany
Accurate results for the testing of combinatorial libraries necessitates
high purity of the library members. Therefore, combinatorial libraries derived
from a combinatorial solution or solid-phase synthesis often require the purification
of compounds that do not achieve a certain purity threshold. This study describes
that preparative high-performance liquid chromatography (HPLC)–mass spectrometry
(MS) is the method of choice for the purification of large arrays of diverse
compounds. The adoption of this technology to the workflow of a solution phase
combinatorial chemistry laboratory producing more than 20,000 compounds per
year is described. Furthermore, the setup and logistics are discussed as well
as the purity achievable for large libraries. Efficiency, speed, quality, and
universality of preparative HPLC–MS are presented in detail for a library
of 140 compounds, including data logistics and downstream processes as well.
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