Bio/Pharmaceutical NEWS - Fall 2011

Mass Spec Lab increases capacity with new equipment, improving chromatographic resolution & TAT

by Jon S. Kauffman, Ph.D., biopharmaceuticals director

Lancaster Laboratories recently acquired two additional time-of-flight (TOF) mass spectrometers. A Waters Xevo G2 TOF, configured with UPLC and Waters new UNIFI software, will be utilized in the Biochemistry Laboratory for protein characterization. This instrument also has a unique upgrade path with the ability to “turn on” the quadrupole mass spectrometer on the front end of the instrument to convert it to a Q-TOF. An Agilent LC/TOF, configured with a 1260 HPLC, will be utilized for extractable/leachable studies and for impurity investigations requiring measurement of accurate mass.

There has been a huge demand from clients for protein characterization, including peptide mapping and intact mass under cGMPs. The UPLC/TOF will allow the Biochemistry Group to take advantage of the smaller particle UHPLC column technology to increase resolution in complicated chromatograms with the potential to shorten run times. The UNIFI software captures complex and comprehensive mass spectrometric and chromatographic (UPLC) data and will allow the Group to acquire, process and report complex LC/MS characterization data more efficiently, while maintaining regulatory compliance. The TOF yields accurate mass information that is critical to protein characterization and allows analysts to accurately determine the masses of high molecular weight proteins and monoclonal antibodies.

Further, a method of data acquisition known as MS^E, which is available on this instrument, collects exact mass precursor and fragment ion information from every detectable component in a sample. Every mass is measured, and spectra for each component are aligned by retention time. MS^E is faster than traditional MS followed by MS/ MS analysis and provides a wealth of information since both MS and MS/MS data for all detectable components in the chromatogram are generated.

Another service area where increasing client demand has necessitated additional capacity and capability is extractable/leachable studies.

The types of components that are tested have evolved over the years. Initially, Lancaster Labs performed a lot of work on packaging materials and metered dose inhaler components; whereas today, much of the work is on disposable (single-use) components used in bioprocessing. The components of interest are exposed to extracted with) a solvent or formulation buffer to determine if any compounds have the potential to “leach” or migrate into the final product. Analyses of the extracts is very mass-spec driven and typically involves GC/MS and LC/MS. GC/MS yields fragmentation patterns or “fingerprints.” Whereas, LC/MS only yields a molecule weight. The accurate mass obtained by the MS TOF will greatly enhance identification capabilities since molecular weight can be determined to a much higher level of precision.