EAS Session Highlights GC/MSD and High-Resolution GC/Q-TOF for Volatile Extractables and Leachables

During the 2024 Eastern Analytical Symposium (EAS), which kicked off November 18 in Plainsboro, New Jersey, scientists from around the globe gather to discuss cutting-edge advancements in analytical chemistry. A session on Monday, titled “Problem Solving with Mass Spectrometry,” focused on how this technique can help in various industries with different approaches.

During this session, Anastasia Andrianova of Agilent Technologies, showed her team’s research into analyzing extractables and leachables identified in rubber gaskets. Extractables are compounds that can be extracted from container closure systems, while leachables are compounds that leach into drug product formulations (1). These substances are contaminants that, left unchecked, can cause impurities of highly valuable drug products. Andrianova’s workshop, “Analysis of Volatile Extractables and Leachables (E&L) Identified in Rubber Gasket Extracts Using GC/MSD and High-Resolution GC/Q-TOF,” showed how gas chromatography (GC)-based techniques could be used in new ways to manage these potentially harmful materials (2).

Rubber Seals Gaskets | Image Credit: © markobe - stock.adobe.com

Modern drug delivery systems aim to protect active pharmaceutical ingredients (APIs) and biologics from degradation. These substances, which are the components of medications that produce the intended health effects, are vital (3). However, when these compounds interact with polymeric components, undesirable impurities may be inadvertently introduced. With this study, a gas chromatography–mass spectrometry (GC–MS)-based workflow that used spectral deconvolution and retention index-based time filtering alongside the expanded NIST24 GC–MS library to identify amenable E&L compounds under a unified compliance environment.

According to Andrianova’s presentation, chemicals derived from pharmaceutical packaging and delivery could migrate into drug products during multiple stages of the process. Gaskets and o-rings are the typical sources for leachable compounds stemming from primary packaging. The team studied rubber gasket extractables using gas chromatography–single quadrupole mass selective detector (GC–MSD) and gas chromatography–quadrupole time-of-flight (GC/Q-TOF), to create a workflow for identifying GC-amenable E&L compounds.

Extraction was performed using a tetrahydrofuran (THF) solvent at room temperature for six months. Two systems were used for this process, including the 5977C GC/MSD system. This system was chosen for its commonality; according to Andrianova, “this is a piece of equipment that, chances are, many of [the audience] have seen at some point through your career. Maybe it was during undergrad, maybe during your graduate studies, maybe in the lab you are working in today” (1). From there, the experimental conditions included a 1 µL injection volume, helium as a carrier gas, and a transfer line temperature of 325 ºC, among others.

Solvent extracts from both the medical devices and drug delivery systems confirmed the presence of phthalate plasticizers, polymerization agents, polycyclic aromatic hydrocarbons (PAHs), and several antioxidants. The scientists also compared the GC–MS-amenable compounds to measure the impact of the extraction solvent and conditions. Preliminary findings showed that the phenyl column, which had measurements of 30 m x 0.25 mm x 0.25 µm with a concentration of 5%, offered sufficient chromatographic resolution and low column bleed levels for identifying low-level compounds.

GC–MSD is an effective and accessible tool for analyzing GC-amenable compounds in complex E&L extracts, Andrianova said. The high-resolution system enabled the identification of additional components with increased confidence and structure elucidations of the unknowns. The data acquired throughout this process was received under a compliant environment. Andrianova and her team also leveraged new columns with decreased bleed levels, allowing for more accurate identification and better longevity for the system.

References

(1) Seifert, D. Extractables and Leachables: Definitions, Differences & Facts. Single Use Support 2022. https://www.susupport.com/knowledge/single-use-consumables/extractables-leachables-definitions-differences-facts (accessed 2024-11-20)

(2) Nieto, S.; Andrianova, A.; Quimby, B.; Weil, D. Analysis of Volatile Extractables and Leachables (E&L) Identified in Rubber Gasket Extracts Using GC/MSD and High-Resolution GC/Q-TOF. In Eastern Analytical Symposium 2024, Plainsboro, NJ, 2024.

(3) Stone, K. What is an Active Pharmaceutical Ingredient (API)? Verywellhealth 2023. https://www.verywellhealth.com/api-active-pharmaceutical-ingredient-2663020 (accessed 2024-11-18)