Alcami Scientists Publish on SIFT-MS & Real-Time Volatiles Analysis for Continuous Pharma Manufacturing

Congratulations to our team of Alcami laboratory services scientists who were recently published in the August edition of the respected LCGC International journal. Chad Bastian, Principal Scientist; Alyssa McBurney, Senior Scientist; and Christopher Williams, Senior Director, Analytical Development are co-authors of the article, Rapid Quantitative Analysis of Ethylene Oxide and 1,4-Dioxane in Polymeric Excipients Using SIFT-MS, which details results of their leading-edge work with SIFT-MS and real-time volatiles analysis for continuous pharmaceuticals manufacturing.

What is SIFT-MS and why is it beneficial?

The pharma industry traditionally favored batch manufacturing, which is relatively small scale and driven by process complexity compared to the rest of the chemical sector. But the industry is facing significant pressures from patients, payers, and healthcare systems which drive increased intricacies in the design, development, manufacturing, and supply of future medicines. Pharma is therefore shifting to continuous manufacturing to improve consistency, reduce operating costs, and implement advanced process control based on real-time measurements.

Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) is a novel direct-injection mass spectrometry technique that addresses continuous manufacturing through real-time, broad-spectrum, high-sensitivity analysis that can be validated according to conventional pharmaceutical industry guidelines. Speed, increased sensitivity, accuracy, and simplicity in sample prep are the major advantages of the technology when compared to conventional gas chromatography (GC), as the team outlines in the study findings.

Ethylene oxide is used as a raw material in the manufacture of polyethylene glycols (PEGs) and polysorbate (trade name Tween) compounds used as solubilizers or stabilizers in pharmaceutical formulations. However, ethylene oxide is an environmental pollutant, is mutagenic to humans and can generate 1,4 -dioxane, a carcinogen linked to organ toxicity. As a result of the problems attributed to ethylene oxide and 1,4-dioxane, pharmaceutical quality requirements include limits on residual ethylene oxide and dioxane.

The findings outlined in the article illustrate that high-sensitivity headspace-SIFT-MS analysis enables linear detection of ethylene oxide and effectively discriminates against its major interferent: acetaldehyde. The LOQ for ethylene oxide was calculated to be 0.5 ppm, which is well below the acceptance criteria outlined in USP <228>. The higher sensitivity of SIFT-MS enables use of 10-fold lower mass of sample compared to GC–FID, enabling 6-hour prep of matrix-matched standards to be eliminated, as the effect from matrix becomes negligible. A single-point calibration using an external standard prepared in water can be used. SIFT-MS successfully measured both ethylene oxide and 1,4-dioxane in several PEG samples, and revealed that “stripped” PEG, which has undergone a rotovap step to remove volatiles, is not volatile-free, as ethylene oxide and 1,4-dioxane were detected in some of the “stripped” PEG samples due to the increased sensitivity provided by SIFT-MS.

Headspace-SIFT-MS analysis of ethylene oxide was found to be 9- to 14-fold faster than the compendial GC–FID method, yielding sample throughputs of up to 224 samples/day. Shorter and simpler sample preparation when combined with faster analysis of SIFT-MS enables delivery of the first test result eight-fold faster than GC–FID.

The article concludes that headspace-SIFT-MS is an industry-proven technology ready for the QA/QC laboratory and process line.

Read the Full Article

Contact our Laboratory Services team to learn more.