Extractable studies: managing LC/MS unknown compounds with an internal database

Simone Carrara, E&L Laboratory Manager, Eurofins BioPharma Product Testing Italy, SimoneCarrara@eurofins.com Andrew Blakinger, Manager, Extractables & Leachables Testing, Eurofins Lancaster Laboratories, AndrewBlakinger@eurofinsus.com

Unknown compound characterisation has always represented one of the most challenging aspects of analytical chemistry. In the Extractables & Leachables (E&L) field, characterisation of unknown extractables is necessary to provide high quality studies.

Accurate and meaningful toxicological assessments are not possible for unknown compounds, which are commonly treated as the most toxic compounds to provide a worst case assessment. Often, this level of risk does not correspond to the compound’s actual toxicological risk. Therefore, a systematic approach to identify unknown extractables is needed to assign the correct degree of toxicological concern.

Unknown compound identification requires experienced analysts, high resolution instrumentation, and dedicated software able to quickly search historical data. Accordingly, Eurofins BioPharma Product Testing continues to invest in LC/MS and GC/MS databases to support their expertise and growth as an E&L service provider. For extractable compounds detected by LC/MS, Eurofins BioPharma Product Testing maintains a proprietary database of over 1,500 compounds.

The first step is to propose an identity using the databases. An attempt is made to confirm the identification by analysing the certified reference standard. If the standard is not commercially available, it may be possible to have it synthesised or to use a chemically-similar surrogate. If an identify cannot be proposed from this initial analysis, an MS/MS study is performed with high resolution mass spectrometers capable of accurate mass determination to at least three decimal places, such as LC-QTOFs and GC-QTOFs, to elucidate the structure based on the fragmentation pathways.

Through the years, Eurofins BioPharma Product Testing has developed the expertise needed to support all phases of an E&L study, including the characterisation of unknown compounds. Eurofins is continuously investing in state-ofthe- art equipment to support clients in this critical area on their path to regulatory approval.

For more information, visit www.Eurofins.com/biopharma