Manufacturing & Analytical Characterization
David Weil, PhD (he/him/his)
Master Applications Scientist
Agilent
Santa Clara, California
Recent changes to medical device testing regulations (ISO-10993-18) and rapid growth of biomanufacturing has expanded the demand for comprehensive Extractable Leachable (E/L) testing resulting in lengthy delays for results from many research testing laboratories. Customers report that the major bottlenecks in E/L testing are 1) sample preparation many times using different extraction solvents, 2) preparing extracts for both GC/MS and LC/MS analysis and 3) the identification of unknowns in these extracts. Herein, we describe the use of Automated solvent extraction system to prepare samples using multiple solvent, temperature, and time conditions. Next, we will review the use of automated liquid sample handling system to prepare samples for GC/MS and LC/MS analysis and describe which compounds should be analyzed using GC/MS and which compounds by LC/MS. The goal of any analysis is to accurately identify target/suspect and unknown compounds in a complex mixture and will discuss why the industry is moving towards the use of high-resolution mass spectrometry collecting LC/MS/MS mass spectral data is critical. Compound identification using both the Agilent 7250 GC/QTOF for the volatile and semivolatile compounds (high and low energy EI) and the Agilent 6546 LC/Q-TOF system interfaced with reversed phase LC separation, using the Agilent Jet Stream Dual ESI source and the Agilent APCI source in both positive and negative polarity modes provides the widest coverage for E/L analysis. Next, the identification of unknowns in Extractable Leachable (E/L) analysis continues to be one of the biggest challenges in the field. Other fields (e.g., food, environmental) benefit from researchers sharing and populating open access online mass spectral repositories, enabling enhanced identification workflows and increased compound coverage. In contrast, E/L testing labs tend to leverage in-house confidential compound databases (DB), making public information sparse and siloed for E/L researchers. Public information pertinent to E/L analysis does exist in technical presentations and publications, such as the ELSIE online DB, NIST and Wiley Mass Spectrometry DB and commercial E/L focused DBs. Herein, we present a new software that enables researchers to generate custom application specific mass spectral libraries and databases for compound identification. To enhance compound identification, we will describe the use Agilent’s new database software (ChemVista) that enables the importing of compound and spectral data using *.SDF, *.csv, *.txt (MassBank), *.cdb (Agilent Personal Compound Database Library, PCDL) formats and by exporting compound lists present in the EPA Chemicals Dashboard in SDF format. Spectral data from MassBank and MassBank of North America also can be directly imported. Compound and chemical structure data is used to combine imported data from all these sources in a compound-centric manner and remove duplicate entries. Efficient sub-setting can be achieved through searching by Identifiers (Name, CAS, etc.), Formulas, and Exact Mass. Complex queries can be conducted combining search types to arrive at targeted sets of compounds. Metadata, RT, and analyzer information can be imported for each compound. Compound and mass spectra can be exported into Agilent PCDL format, SDF or MassBank formats to support a variety of identification workflows.