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.

一种局部浇注药物产品形成淡黄色，并在产品的保质期内继续增加强度。这导致药品颜色的超标 (OOS) 结果。根据使用高效液相色谱、高分辨率质谱和测色分光光度计获得的实验结果，确定 OOS 样品中颜色形成的根本原因并确认为 3,3',5,5' -四叔丁基-4,4'-芪醌 (2BHT-QM)，t的氧化降解产物-丁基化羟基甲苯 (BHT)，在该药品中用作抗氧化剂。通过两种独立的分析方法估计 OOS 样品中 2BHT-QM 的含量约为 0.9-1 ppm。我们的调查结果清楚地表明，BHT 会导致液体或半液体制剂（药物产品）的颜色变化，这是我们首次报告。当 BHT 用于液体或半液体制剂时，本文中描述的调查方法和基本原理应该有助于类似的调查。