Chemical analysis for leachables is one of the the primary methods used to assess the risk to patients and consumers from substances which leach from pharmaceutical packaging, medical devices and food packaging. A number of high-profile incidents have demonstrated that leachables can have significant adverse effects on product safety and can also result in product recalls. The most widely publicized example of this is the migration of bisphenol A from baby bottles but examples related to food contact applications (cereal packaging) and children’s medication have also been reported.[1],[2],[3]

The foundation of the chemical analysis and risk assessment process for Extractables and Leachables (E&L) is the accurate identification and quantification of species in the leachables solutions. Accurate identification and quantification of leachables is crucial if an appropriate toxicological evaluation is to be performed. Identification and quantification are both challenging areas of analytical science due to the wide variety of extractables and potential leachables, the complexity of many leachables solutions and the lack of suitable reference standards.

The industry has approached this last problem, lack of reference standards, by using relative quantitation with surrogate standards. This can result in errors in quantitation due to response factor variation, i.e. different detector responses for compounds present at the same concentration. In this presentation, we will report the results of a systematic study of the response factors for E&L compounds. Response factor variation was studied using three different detector systems (LCMS, UV, CAD) and the deviation in response factors by each detector was compared to determine which detectors are most universal and for which compound classes.

A comparison of the stability of the response factors on multiple LCMS-UV-CAD systems was also performed to determine if response factor databases created on one instrument platform can be migrated to other platforms without creating additional error. The overall effect of response factor variation on quantitative accuracy will be highlighted and recommendations will be given for the optimum detector configurations to minimize quantitative error.

[1]Update on Bisphenol A for Use in Food Contact Applications: January 2010.

[2] Kellogg Company Voluntarily Recalls Select Packages of Kellogg’s® Corn Pops®, Kellogg’s® Honey Smacks®, Kellogg’s® Froot Loops® and Kellogg’s® Apple Jacks®.

[3] McNeil Consumer Healthcare Announces Voluntary Recall of Certain Over-The-Counter (OTC) Products in the United States, Fiji, Guatemala, Dominican Republic, Puerto Rico, Trinidad & Tobago, and Jamaica.


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