Development of an analytical method to assess the occupational health risk of therapeutic monoclonal antibodies using LC-HRMS
Monoclonal antibodies are a group of commonly used therapeutics, whose occupational health risk is still discussed controversially. The long-term low-dose exposure side effects are insufficiently evaluated; hence, discussions are often based on a theoretical level or extrapolating side effects from therapeutic dosages. While some research groups recommend applying the precautionary principle for monoclonal antibodies, others consider the exposure risk too low for measures taken towards occupational health and safety. However, both groups agree that airborne monoclonal antibodies have the biggest risk potential. Therefore, we developed a peptide-based analytical method for occupational exposure monitoring of airborne monoclonal antibodies. The method will allow collecting data about the occupational exposure to monoclonal antibodies. Thus, the mean daily intake for personnel in pharmacies and the pharmaceutical industry can be determined for the first time and will help to substantiate the risk assessment by relevant data. The introduced monitoring method includes air sampling, sample preparation and detection by liquid chromatography coupled with high-resolution mass spectrometry of individual monoclonal antibodies as well as sum parameter. For method development and validation, a chimeric (rituximab), humanised (trastuzumab) and a fully humanised (daratumumab) monoclonal antibody are used. A limit of detection between 1 μg per sample for daratumumab and 25 μg per sample for the collective peptide is achieved.
KeywordsMonoclonal antibody Occupational exposure Sensitising High-resolution mass spectrometry Airborne Sum parameter
We thank Agilent Technologies and especially Dr. Bita Kolahgar for providing the HPLC-QTOF system and the technical support.
Compliance with ethical standards
Conflict of interest
The authors declare they have no conflict of interest.
- 3.Brian A. Baldo, (2017) Safety of biologics therapy: monoclonal antibodies, cytokines, fusion proteins, hormones, enzymes, coagulation proteins, vaccines, botulinum toxins, 1st Edition, Springer, 2016, Print Book ISBN: 978-3-319-30470-0, e-Book ISBN 978-3-319-30472-4. Drug Saf 40 (10):933–934.Google Scholar
- 7.Carter PJ, Lazar GA. Next generation antibody drugs: pursuit of the high-hanging fruit. Nat Rev Drug Discov. 2017; https://doi.org/10.1038/nrd.2017.227.
- 10.Langford S, Fradgley S, Evans M, Blanks C. Assessing the risk of handling monoclonal antibodies. Hosp Pharm. 2008;15:60–4.Google Scholar
- 12.Bos JD, Meinardi M. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9. https://doi.org/10.1034/j.1600-0625.2000.009003165.x.CrossRefGoogle Scholar
- 17.Halsen G, Krämer I. Bewertung monoklonaler Antikörper zum Schutz Beschäftigter. Berufsgenossenschaft für Gesundheitsdienst und Wohlfahrtspflege. Germany: Hamburg; 2008.Google Scholar
- 18.Promega. Sequencing grade modified trypsin: product information. 2016 https://www.promega.com/-/media/files/resources/protocols/product-information-sheets/n/sequencing-grade-modified-trypsin-protocol.pdf?la=en. Accessed 28.11.17.
- 19.Mandel J. The statistical analysis of experimental data. Washington: Wiley; 1964.Google Scholar
- 24.Nowak C, Cheung J, Dellatore S, Katiyar A, Bhat R, Sun J, Ponniah G, Neill A, Mason B, Beck A, Liu H. Forced degradation of recombinant monoclonal antibodies: a practical guide. mAbs. 2017; 1–14. https://doi.org/10.1080/19420862.2017.1368602.
- 28.Paul-Ehrlich-Institut. Monoklonale Antikörper. 2017 http://www.pei.de/DE/arzneimittel/immunglobuline-monoklonale-antikoerper/monoklonale-antikoerper/monoklonale-antikoerper-node.html. Accessed 28.11.17.
- 30.ISPE. Good practice guide: assessing the particulate containment performance of pharmaceutical equipment. 2nd ed. Bethesda: International Society for Pharmaceutical Engineering; 2012.Google Scholar