Application of Routine Analysis Procedures to a Direct Mass Spectrometry Technique: Selected Ion Flow Tube Mass Spectrometry (SIFT-MS)

In recent years the environmental and human health impacts of volatile organic compounds (VOCs) have become more apparent, resulting in increased analysis demand. The gold-standard chromatographic techniques continue to be employed for most laboratory analyses. However, they have made only modest gains in productivity over the years, and these gains are primarily due to automated sample preparation and injection. Alternatively, significant productivity gains for VOC analysis through faster sample analysis and reduced instrument maintenance could be achieved by adopting direct mass spectrometry techniques such as selected ion flow tube mass spectrometry (SIFT-MS). This article demonstrates that routine analysis techniques such as quality control checks, method validation, the method of standard additions, and internal standards are readily applied to SIFT-MS, simplifying adoption of the technique. In addition, workflows for analysis of chromatographically challenging species are simplified by using SIFT-MS. Sample throughputs are increased two- to 25-fold depending on the analytical procedure.

Importance of a High Performing GC-MS Based Screening Method for Testing Stability Samples for Volatile and Semi-Volatile Leachable Impurities

Leachable testing for finished pharmaceutical products is an important part of the regulatory filing and is under more regulatory scrutiny than ever before. Leachable testing for multiple finished drug products such as biologics, large volume parenterals, and polymer-based finished products requires analysis at trace levels with a high level of confidence. A high level of analytical expertise and top-of-the-line analytical instrumentation is required for work at trace levels. (The definition of trace level analytical testing has not been accurately defined; however, to have a sense of the “trace-level”-associated testing issues, we are arbitrarily assigning levels below 100 ng/mL as trace level and below 1 ng/mL as ultra-trace level in this paper). Leachable testing ideally should be performed on a targeted list of analytes compiled from an extractable study and an extractable and leachable correlation study, along with a general non-targeted screening evaluation to avoid any undetected leachables. For targeted screening, analytical testing is more straightforward and can typically detect targets at ppb or sub-ppb levels without issue. However, for a general screening method, this can be difficult, and many times requires special sample preparation combined with high-resolution accurate-mass detection. Case studies will be presented to demonstrate the importance of high-performance and highly sensitive screening methods in detecting unexpected leachables, and in supporting related quality investigations. The importance of well-designed and executed system suitability will also be discussed in this paper.