ABSTRACT
Tinuvin 770 is a light stabilizer present in numerous polymers utilized in medical or pharmaceutical applications (e.g., manufacturing, packaging, delivery systems and devices). Under conditions of use, Tinuvin 770 and its related substances may leach from the polymers and accumulate in pharmaceutical products that are administered to subjects to produce a therapeutic benefit. In order to establish the amounts of Tinuvin 770 that may be extracted from such systems and devices, sensitive and selective analytical methodologies are required. A liquid chromatographic method with tandem mass spectrometric detection (LC-MS-MS; API-ES, positive ion mode) has been developed for the purpose of quantitating Tinuvin 770 and a related substance at low concentrations [200 ng/mL (ppb) or less] in aqueous extracting media. Issues related to injection-to-injection carryover and sample matrix effects were mitigated by the addition of potassium chloride to the test samples, where the potassium ion increases Tinuvin solubility via a "salting in" effect. The developed method was validated for this application by assessing performance characteristics including accuracy, response linearity, precision, specificity, and solution stability. The validated method is suitable for the quantitation of these analytes in the concentration range of 1-200 ng/mL.
Subject(s)
Chromatography, High Pressure Liquid/methods , Decanoic Acids/analysis , Piperidines/analysis , Plastics/chemistry , Tandem Mass Spectrometry/methods , Decanoic Acids/chemistry , Linear Models , Piperidines/chemistry , Sensitivity and SpecificityABSTRACT
Plastic materials are widely used in medical items, such as solution containers, transfusion sets, transfer tubing, and devices. An emerging trend in the biotechnology industry is the utilization of plastic containers to prepare, transport, and store an assortment of solutions including buffers, media, and in-process and finished product. The direct contact of such containers with the product at one or more points in its lifetime raises the possibility that container leachables may accumulate in the finished product. The interaction between several commercially available container materials and numerous model test solutions (representative of buffers and media used in biopharmaceutical applications) was investigated. This paper summarizes the identification of leachables associated with the container materials and documents the levels to which targeted leachables accumulate in the test solutions under defined storage conditions.
Subject(s)
Drug Contamination/prevention & control , Drug Packaging/instrumentation , Drug Storage , Organic Chemicals/analysis , Plastics/chemistry , Acetates/analysis , Amides/analysis , Buffers , Chromatography, Ion Exchange , Chromatography, Liquid , Equipment Design , Fatty Acids/analysis , Formates/analysis , Hydrogen-Ion Concentration , Mass Spectrometry , Reproducibility of Results , Spectrophotometry, UltravioletABSTRACT
Container/closure systems are extensively characterized in terms of their propensity to contribute leachable substances to the drug products they contain. Such a characterization is relevant until a change occurs in the composition or production of the container/closure system itself or the raw materials it is comprised of. When such a change occurs, it is necessary to ascertain the impact that the change would have on the validity and applicability of the previously performed leachables assessment. A general methodology for performing change control evaluations is developed in this manuscript and is illustrated via the use of a case study.
