Isolation, structural determination, synthesis and quantitative determination of impurities in Intron-A, leached from a silicone tubing

Journal of Pharmaceutical and Biomedical Analysis
Tze-Ming ChanVinod Hegde

Abstract

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.

References

Aug 10, 2007·Journal of Pharmaceutical and Biomedical Analysis·Russell G MausJeffery A Kinzer

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Citations

May 24, 2014·Journal of Pharmaceutical and Biomedical Analysis·Rubén M MaggioTeodoro S Kaufman
May 31, 2012·Journal of Pharmaceutical Sciences·Ning LiWei Wang
Jul 2, 2016·The Journal of Pharmacy and Pharmacology·Verena SallerWolfgang Friess

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