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Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut, john.watson{at}bms.com

Emily B. Greenough

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

John E. Leet

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

Michael J. Ford

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

Dieter M. Drexler

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

James V. Belcastro

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

John J. Herbst

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

Moneesh Chatterjee

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

Martyn Banks

Bristol-Myers Squibb Company, Research and Development, Wallingford, Connecticut

Disposable plastic labware is ubiquitous in contemporary pharmaceutical research laboratories. Plastic labware is routinely used for chemical compound storage and during automated liquid-handling processes that support assay development, high-throughput screening, structure-activity determinations, and liability profiling. However, there is little information available in the literature on the contaminants released from plastic labware upon DMSO exposure and their resultant effects on specific biological assays. The authors report here the extraction, by simple DMSO washing, of a biologically active substance from one particular size of disposable plastic tips used in automated compound handling. The active contaminant was identified as erucamide ((Z)-docos-13-enamide), a long-chain mono-unsaturated fatty acid amide commonly used in plastics manufacturing, by gas chromatography/mass spectroscopy analysis of the DMSO-extracted material. Tip extracts prepared in DMSO, as well as a commercially obtained sample of erucamide, were active in a functional bioassay of a known G-protein-coupled fatty acid receptor. A sample of a different disposable tip product from the same vendor did not release detectable erucamide following solvent extraction, and DMSO extracts prepared from this product were inactive in the receptor functional assay. These results demonstrate that solvent-extractable contaminants from some plastic labware used in the contemporary pharmaceutical research and development (R&D) environment can be introduced into physical and biological assays during routine compound management liquid-handling processes. These contaminants may further possess biological activity and are therefore a potential source of assay-specific confounding artifacts.

Key Words: compound management • plastic • extractables • leaching • erucamide

This version was published on June 1, 2009

Journal of Biomolecular Screening, Vol. 14, No. 5, 566-572 (2009)
DOI: 10.1177/1087057109336594


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