This study aimed to evaluate the compatibility of generic ceftriaxone sodium preparations with various rubber closures used in pharmaceutical packaging, focusing on the release of butylated hydroxytoluene (BHT), an antioxidant present in rubber closures that may migrate into drug products. BHT levels were quantified using gas chromatography-mass spectrometry (GC-MS) to assess stability and safety. Results showed that all samples contained BHT, with concentrations ranging from below the quantification limit to a maximum of 5.65 ppm. Notably, 47.62% of the samples exceeded the threshold of toxicological concern (TTC) of 1.5 µg/day, raising significant safety concerns. Older samples exhibited higher BHT levels, and products from pharmacies generally had greater concentrations than those obtained from manufacturers. These findings underscore the critical importance of assessing interactions between drug formulations and packaging materials, emphasizing the need for rigorous quality control in injectable pharmaceuticals. Future research should explore strategies to mitigate BHT accumulation in these preparations.