Isolation, structural determination, synthesis and quantitative determination of impurities in Intron-A, leached from a silicone tubing
| Autor: | Bart Cronin, Christopher W. Boyce, Mike Berlin, Birendra N. Pramanik, Peter L. Bartner, Mccormick Kevin D, Larry Heimark, Mahesh Patel, Tze-Ming Chan, Vincent P. Gullo, Alexei V. Buevich, Haiyan Pu, Guodong Chen, Xiaohong Zhu, Robert G. Aslanian, Vinod R. Hegde |
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| Rok vydání: | 2009 |
| Předmět: |
Quality Control
Magnetic Resonance Spectroscopy Time Factors Chemistry Pharmaceutical Clinical Biochemistry Silicones Pharmaceutical Science Buffers Interferon alpha-2 Chemical synthesis High-performance liquid chromatography Mass Spectrometry Analytical Chemistry Freeze-drying chemistry.chemical_compound Impurity Phase (matter) Drug Discovery Humans Organic Chemicals Chromatography High Pressure Liquid Spectroscopy Biphenyl Aqueous solution Chromatography Molecular Structure Temperature Interferon-alpha Hydrogen-Ion Concentration Recombinant Proteins Freeze Drying chemistry Powders Drug Contamination Quantitative analysis (chemistry) |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 49:327-332 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2008.11.038 |
| Popis: | Investigation of unexpected levels of impurities in Intron product has revealed the presence of low levels of impurities leached from the silicone tubing (Rehau RAU-SIK) on the Bosch filling line. In order to investigate the effect of these compounds (1a, 1b and 2) on humans, they were isolated identified and synthesized. They were extracted from the tubing by stirring in Intron placebo at room temperature for 72 h and were enriched on a reverse phase CHP-20P column, eluting with gradient aqueous ACN and were separated by HPLC. Structural elucidation of 1a, 1b and 2 by MS and NMR studies demonstrated them to be halogenated biphenyl carboxylic acids. The structures were confirmed by independent synthesis. Levels of extractable impurities in first filled vials of actual production are estimated to be in the range of 0.01-0.55 microg/vial for each leached impurity. Potential toxicity of these extractables does not represent a risk for patients under the conditions of clinical use. |
| Databáze: | OpenAIRE |
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