Structural identification of extractables from rubber closures used for pre-filled semisolid drug applicator by chromatography, mass spectrometry, and organic synthesis

Investigation of Drug-Packaging Interactions with Mass Spectroscopy Detectors: A Meta-Synthesis of the Literature

“…Among the 32 articles included in this meta-synthesis of E/L contamination, 18 identification studies and 14 quantification studies were flagged (Tables 1-2) [6,7,9,11,13,.…”

“…MS is frequently used for E/L analysis because it allows structural, qualitative, and quantitative analyses [12]. In fact, MS offers the possibility of identifying unknown compounds thanks to the existence of MS/MS spectral libraries [13].…”

On Developing a Process for Conducting Extractable–Leachable Assessment of Components Used for Storage of Biopharmaceuticals

“…29 For example, refluxing with extraction solvents for 8 h was reported for extraction studies on rubber stoppers. 32,33 As demonstrated by different research groups, due to the variety of chemical species that can be extracted from a component, different analytical methods are required to obtain a complete extractable profile. 24,32,34 Typically, analytical methods such as GC-MS, Headspace (HS) GC-MS, LC-MS, NMR, and ICP-MS may be utilized to characterize leachables.…”

“…32,33 As demonstrated by different research groups, due to the variety of chemical species that can be extracted from a component, different analytical methods are required to obtain a complete extractable profile. 24,32,34 Typically, analytical methods such as GC-MS, Headspace (HS) GC-MS, LC-MS, NMR, and ICP-MS may be utilized to characterize leachables. An example of extractable assessment of bioprocess bags is shown in Table 2 where different solvents ranging from water to 10% (w/v) polysorbate were employed in the extraction study.…”

Development and validation of HPLC methods for the determination of potential extractables from elastomeric stoppers in the presence of a complex surfactant vehicle used in the preparation of parenteral drug products

“…A number of analytical methods have been reported in the literature to quantitate and characterize stopper extractables found in parenteral drug products. These include LC [12,[19][20][21]; LC-MS [20,22,23]; TLC [24]; GC-MS [19]; and atomic absorption spectroscopy [21]. The majority of these methods were applied to stopper ingredients extracted into aqueous product media and, therefore, not subject to matrix challenges posed by more complex formulations such as limitations to sensitivity and reproducibility.…”