Utilization of Internal Standard Response Factors to Estimate the Concentration of Organic Compounds Leached from Pharmaceutical Packaging Systems and Application of Such Estimated Concentrations to Safety Assessment

Abstract

Substances from packaging systems that are leached into packaged medical products may have a safety impact on patients to whom such medical products are administered. The potential safety impact depends on the identity and concentration of the leached substances. The concentration above which a leachable must be identified in order to assess its safety impact is frequently estimated using an internal standard to "calibrate" the analytical response of a chromatographic system. Such an estimate is accurate to the extent that the responses of the internal standard and leachables are similar. To establish the accuracy of the internal standard approach, a database of gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) responses was generated for thirty-eight leachables and eight internal standard candidates. Although the FID and MS responses of many of the leachables and internal standards fell within a narrow band, acidic and basic compounds produced responses that were discernibly different from those of neutral analytes. While most of the internal standards were suited for concentration estimation, three of the candidates, dimethylphthalate, triphenylphosphate and 4,4-dibromobiphenyl, produced the smallest mean error in estimated concentration for the analytes examined. As the FID and MS responses were linear, internal standards could be used to estimate leachables concentrations even when the difference in leachable versus internal standard concentrations was as great as a factor of 25. A multiplier may be appropriate to adjust an estimated concentration to its greatest possible value, and it is this value that is used to convert an estimated Analytical Evaluation Threshold (AET) into a working or final AET.

Chemical Characterization and Non-targeted Analysis of Medical Device Extracts: A Review of Current Approaches, Gaps, and Emerging Practices

“…Flame ionization detectors (FIDs) are used as supplemental detectors to MS in GC analysis due to their orthogonal detection mechanism. For example, GC coupled with FID has been used for the analysis of residual solvents and as a supplementary/complementary analytical approach to GC/MS for quantifying analytes. ,, …”

Multistage Chemical Recycling of Polyurethanes and Dicarbamates: A Glycolysis–Hydrolysis Demonstration

“…Ethylene glycol in not visible on chromatograms since it was eluted together with solvent at the beginning. In order to obtain quantitative information, an internal standard was used, and relative response factors (RRF) for the amine and polyol or alcohol were calculated, In order to obtain quantitative information, an internal standard was used, and the relative response factors (RRF) for the amine and polyol or alcohol were calculated, due to the weak response factor of amine in comparison to that for the polyol or alcohol [51]. In the first step, the relative response factors for aniline, phenylene diamine, 1-hexanol, and 1,6-hexanediol were calculated.…”

Saturation of thylakoid‐associated fatty acids facilitates bioenergetic coupling in a marine diatom allowing for thermal acclimation

“…Each FAME species was identified by comparing the mass spectrum to the National Institute of Standards and Technology 11 library. The relative abundance of each FAME species was corrected for extraction efficiency and quantified (Jenke & Odufu, 2012) by referencing to an added internal standard, heptadecanoic acid (Sigma-Aldrich), and expressed as molecular percentage of total fatty acid. The double bond index (DBI) and average chain length were determined with all detectable fatty acid species as described (Figure 1a; Figure S1; Feijão et al, 2017).…”