Introduction: Leaching occurs under normal storage conditions, when chemicals from a delivery device or packaging migrate into a drug substance, potentially impacting its safety or efficacy. Consequently, regulatory bodies often require in-depth analytical investigations into the leachable profile of a drug product’s packaging components to ensure patient safety. Often an extractables (chemicals that can be forced out of a device or packaging) investigation is done in conjunction with, or prior to, a leachables study in order to get a full profile of the potential hazards associated with a medical product.
Case Study, Overview: A client approached EKG Labs with bottles of their pharmaceutical product in both a liquid and gel form. EKG Labs had previously provided extractables and leachables testing on the client’s plastic bottles, but now the client was concerned about new label options for these bottles, particularly in light of growing regulatory concern about potential leachables from adhesives and inks. The client provided samples of these labels as well as filled bottles with and without the labels applied.
Case Study, Part 1: The labels were extracted in both hexane and 50% isopropyl alcohol in water alongside method controls. Sample and control extracts were analyzed via LC/MS, GC/MS, and ICP/MS.
Results: From the LC/MS and GC/MS data, several impurity peaks not found in the controls were observed for the label extractions. Additional mass spectral analysis was performed to identify these extractable components.
LC/MS Control Extraction:
LC/MS Label Extraction:
From an ICP/MS scan of USP <232>/<233> elements of interest, only chromium was observed above quantitation limits and above the control extraction level.
Case Study, Part 2: EKG Labs developed sample preparation methods for both the liquid and gel drug products which had been stored under accelerated stability conditions for one month. Control samples were also prepared under identical conditions from unlabeled bottles. These preparations were analyzed by LC/MS and GC/MS.
Conclusion: Even within challenging matrices, EKG Labs met the client target of quantifying down to 5 µg of impurities in 1 gram of gel by LC/MS and of liquid by GC/MS. With a focus on the extractables known to originate from the labels, no peaks were observed by either LC/MS or GC/MS which were not observed in the control for both products. The client was satisfied that the change in labels used will not affect their drug product.
LC/MS Gel Control:
LC/MS Gel w/ Label:
LC/MS Liquid Control:
LC/MS Liquid w/ Label:
About EKG Labs
EKG Labs performs thorough extractable and leachable testing for a variety of industries such as combination products, medical devices, pharmaceuticals, and consumer products. If you are experiencing a challenge with impurities or need analytical services to support your product development, please contact us at 810-354-5229 to find out how we can help you.
EKG Labs is an analytical service provider for the medical device and pharmaceutical industries. Our analytical services support regulatory filings, product development, and analytical chemistry investigations. Specialty analytical services include: extractables, leachables, impurity identification, method development, method validation, and other investigational activities. EKG Labs is a certified woman-owned business enterprise that operates out of Innovative Technology Enterprises (ITE) at the University of Missouri, St. Louis (UMSL).