Abstract
BACKGROUND: In the last decade biopharmaceuticals became increasingly important. In 2016, nine out of 10 top-selling drugs were classified as biologics and their market share is still growing. The risk assessment of biopharmaceuticals from the occupational health perspective, however, is not completed. Especially the role of therapeutic monoclonal antibodies (mAbs) for occupational safety is still discussed controversially. In this debate it becomes clear that the large molecular weight hinders mAbs to penetrate the skin and diminishes the pulmonary uptake. Thus only slight amounts of mAbs reach systemic circulation. Nevertheless, sensitisation by pulmonary uptake cannot be excluded. However, the major problem in this discussion is the lack of data about the effects at long-term low dose exposure. Thus, the occupational risk is still uncertain. Besides that theoretical examination the effective airborne mAbs exposure to healthcare staff is not monitored. PURPOSE: We have developed a method that enables the measurement of airborne mAbs. A sensitive analytical method is crucial for assessing the effective personnel exposure. Therefore, in a first step the stability of mAbs, the sampling rate and the limit of detection for several mAbs were investigated. MATERIAL AND METHODS: In our study rituximab, trastuzumab and daratumumab were analysed. High-performance liquid chromatography, coupled to high resolution mass spectrometry (LC-HRMS), was used to estimate the mAb concentration after tryptic digestion. RESULTS: It is shown that >85% of the mAbs are recovered when sampled up to 24 hours. Depending on the respiratory volume the sampling rate was set to 2 L min(-1), resulting in 1 m(3) per working shift (8 hours). The limit of detection (LOD) for signature peptides varies from 5 to 10 µg per m(3). For the overall peptide the LOD is 26 µg. CONCLUSION: A method based on LC-HRMS to detect airborne mAbs was successfully developed and validated. Furthermore, a suitable personnel sampling method was identified. It is expected that airborne mAbs reach concentrations up to several micrograms per working shift. Thereby, our method achieves the relevant measurement range. Otherwise, it is necessary to transfer the method to a more sensitive LC-MS/MS detection system to achieve even lower detection limits. No conflict of interest