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Investigation to Identify the Root Cause of Out-of-Specification Results for Color of a Topical Pour-on Drug Product: A Case Study

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Abstract

One topical pour-on drug product formed a slightly yellow color and continued to increase the intensity over the shelf life of the product. This caused out-of-specification (OOS) results for the color of the drug product. Based on the experimental results obtained using high-performance liquid chromatography, high-resolution mass spectrometry, and a color measurement spectrophotometer, the root cause of color formation in the OOS sample was identified and confirmed to be 3,3′,5,5′-tetra-t-butyl-4,4’-stilbenequinone (2BHT-QM), an oxidative degradation product of t-butylated hydroxytoluene (BHT) which is used in this drug product as an antioxidant. The content of 2BHT-QM in the OOS sample was estimated to be about 0.9–1 ppm by two independent analytical methods. The results from our investigation clearly indicated that BHT can cause color change in liquid or semi-liquid formulation (drug product) and we report this for the first time. The investigation approach and rationale of described in this paper should be helpful for similar investigations when BHT is used in liquid or semi-liquid formulations.

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Authors and Affiliations

  1. Global Pharmaceutical Technical Support, Boehringer Ingelheim Animal Health (BIAH) USA Inc, North Brunswick, NJ, 08902, USA

    Daoli Zhao, Lin Wang, Rasangi M. Wimalasinghe, Jingzhi Tian & Abu Rustum

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  1. Daoli Zhao
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  2. Lin Wang
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  3. Rasangi M. Wimalasinghe
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  4. Jingzhi Tian
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Correspondence to Jingzhi Tian.

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Zhao, D., Wang, L., Wimalasinghe, R.M. et al. Investigation to Identify the Root Cause of Out-of-Specification Results for Color of a Topical Pour-on Drug Product: A Case Study. Chromatographia 84, 905–915 (2021). https://doi.org/10.1007/s10337-021-04077-0

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