title: Quality control in combinatorial chemistry: determination of the quantity, purity, and quantitative purity of compounds in combinatorial libraries.
abstract: The quality of combinatorial libraries determines the success of biological screening in drug discovery programs. In this paper, we evaluate and compare various methods for measuring identity, purity, and quantity (yield) of combinatorial libraries. Determination of quantitative purity reveals the true library quality and often indicates potential quality problems before full-scale library production. The relative purity can be determined for every member in a large library in a high-throughput mode, but must be cautiously interpreted. In particular, many impurities are not observable by relative purity measurements using detectors such as UV(214), UV(254), and evaporative light-scattering detection. These "invisible" impurities may constitute a significant portion of the sample weight. We found that TFA, plastic extracts, inorganic compounds, and resin washout are among these impurities. With compelling evidence, we reach a conclusion that purification is the only way to remove "invisible" impurities and improve the quantitative purity of any compound even though some compounds may have a high relative purity before purification.
authors.affiliation: ChemRx Division, Discovery Partners International, Inc., 385 Oyster Point Boulevard, South San Francisco, California 94080, USA. byan@chemrx.com
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Liling
authors.initials: L
authors.lastname: Fang
authors.forename: Mark
authors.initials: M
authors.lastname: Irving
authors.forename: Sue
authors.initials: S
authors.lastname: Zhang
authors.forename: Armen M
authors.initials: AM
authors.lastname: Boldi
authors.forename: Frank
authors.initials: F
authors.lastname: Woolard
authors.forename: Charles R
authors.initials: CR
authors.lastname: Johnson
authors.forename: Tushar
authors.initials: T
authors.lastname: Kshirsagar
authors.forename: Gianine M
authors.initials: GM
authors.lastname: Figliozzi
authors.forename: Clinton A
authors.initials: CA
authors.lastname: Krueger
authors.forename: Nathan
authors.initials: N
authors.lastname: Collins
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods / Q000592:standards*; D004340:Drug Contamination; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000592:standards*; D011786:Quality Control
chemical_list: D004364:Pharmaceutical Preparations