Using X-ray fluorescence to measure inorganics in biopharmaceutical raw materials

摘要

Small deviations in metal content found in biopharmaceutical raw materials can have detrimental effects on cell culture activity and growth. Here we report the use of a portable energy-dispersive X-ray fluorescence (EDXRF) spectrometer for elemental analysis of powdered raw materials (hydrolysates and chemically defined media) to help maintain consistent therapeutic protein quality and production. Unlike traditional metal analysis techniques such as inductively coupled plasma mass spectrometry (ICP-MS), EDXRF analysis requires no sample preparation and acquisition times range from 2 to 10 minutes for a sub-ppm limit of detection for elements such as Cu and Zn. However, issues with sensitivity, matrix interferences and calibration standards have prevented EDXRF from being adopted in the biopharmaceutical industry. This paper presents an alternative method to overcome these limitations, involving: measuring raw materials before dilution to ensure the largest metal concentration; the use of wavelet transforms to process EDXRF spectra, removing background and matrix variability; and utilizing the resultant spectral intensity to correlate to cell culture process parameters before developing calibration standards. Finally, a brief case study will outline the methodology and illustrate the high throughput of the EDXRF spectrometer for identifying the raw material and quantifying the key trace metal associated with process attributes.