The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic. Graphical Abstract ᅟ.

Site-specific characterization of the N- and O-linked glycosylation on a set of different human chorionic gonadotropin (hCG) drug products was performed by a LC-MS method combining high resolution (120K at m/z 200) mass spectrometry, multiple dissociation methods, tandem mass tag (TMT 10plex) labeling, and partial least squares-discriminant analysis (PLS-DA). In total, the data provided identification, relative quantification, and comparison of site-specific glycosylation of protein therapeutics with a single experiment. Ten different lots and/or brands of commercial therapeutic hCG were labeled with TMT 10plex reagents after tryptic digestion. The labeled intact glycopeptides were then analyzed by high resolution LC-MS with online alternating HCD/ETD/CID dissociation methods. For digested hCG drugs, 1000 intact N- and O-linked glycopeptides were identified. The relative amount of each glycopeptide from hCG products was determined based on the reporter signal intensities of the TMT labeling reagents. Moreover, with the help of TMT 10plex, through just one LC-MS run, PLS-DA was performed to ascertain the differences in glycosylation among different sources of hCG drug products. The results of PLS-DA showed that 167 glycopeptides were found to be significantly different between the naturally derived and recombinant hCG products. The results demonstrate the suitability of this method for similarity assessments and counterfeit identification of hCG as well as other glycoproteins.

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In this paper we describe the use of ion mobility spectrometry (IMS) and liquid chromatography – high resolution mass spectrometry (LC-HRMS) to screen for the presence of cannabinoids and other potential hazards in a set of products with hemp oil and/or cannabinoid label claims purchased via the internet. Preliminary screening was performed using IMS to examine the products for the presence of cannabinoids, illicit drugs or undeclared pharmaceuticals before analysis by LC-HRMS to quantitatively determine the presence of four of the most common naturally occurring cannabinoids while simultaneously qualitatively screening for the presence of nine of the most common cannabinoids.  No other illicit drug or undeclared pharmaceutical was detected in any sample from IMS screening. Eighteen of twenty-three samples tested positive for the presence of at least one cannabinoid by LC-HRMS, with  three products containing less than 0.01%(w/w) of a cannabinoid. Four products with explicit CBD label claims were found to not contain any CBD, while three products featured levels of cannabinoids below label claim.https://doi.org/10.21423/jrs-v04n03p001 (DOI assigned 5/31/2019)