Although the secondary packing materials do not directly contact the finished drug products, compound migration may still happen between them. To ensure drug quality and safety, extractables and leachables of the packing materials should be analyzed. In this study, 2,6-di-tert-butyl-4-methylphenol (BHT) was first found in the labels for pharmaceutical packaging. For the identification of the compound, a strategy combining high performance liquid chromatography (HPLC), ultra-performance liquid chromatography-quadrupole time-of-flight mass (UPLC-Q-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy was utilized. Afterwards, a effective and sensitive HPLC method for quantification of BHT was developed and validated. Finally, a toxicological risk assessment of BHT was performed to ensure the safety of drugs.
A simple and efficient method involving microwave-assisted extraction (MAE) combined with GC–MS was established to determine 1,3-di- tert -butylbenzene (DBB), 2,4-di- tert -butylphenol (DBP), 3,5-di- tert -butyl-4-hydroxybenzaldehyde (DBHBA) for evaluating the compatibility of antimicrobial peptide PL-5 spray with drug-packaging materials. In this study, the antimicrobial peptide PL-5 spray was purified using a Welchrom C18 column, and the high-density polyethylene spray bottle with liquid collection tube was first mixed with absolute ethanol, which would be subjected to MAE for further measurement by GC–MS. Various experimental parameters were systematically optimized, and good linearities were obtained within the range of 0.05–1.00 μg/mL for DBB and DBHBA and 0.50–10.00 μg/mL for DBP, with limits of detection (LODs) of 0.99 ng/mL (DBB), 16.34 ng/mL (DBP), and 1.64 ng/mL (DBHBA). Satisfactory recoveries that ranged from 96.0% to 107.2% were acquired, and the relative standard deviation was ≤ 4.7%. The results showed that the maximum daily usage of DBB, DBP, and DBHBA was 9.859, 163.445, and 16.399 ng, respectively, which was far below the corresponding permitted daily exposure values according to the safety assessment, indicating that the migration of analytes did not bring any potential safety risk. The compatibility between the drug and the packaging materials was favorable.
Liming Ge,Mingjin Zhu,Xinying Li,Yongbin Xu,Xiaonan Ma,Rong Shi,Defu Li,Changdao Mu
It is significant to develop new approaches to incorporate naturally active agents into gelatin-based edible films for effective antioxidant and long-term antibacterial activities. Here the naturally active compound rosmarinic acid (RosA) was firstly conjugated onto gelatin backbone via EDC/NHS chemistry. Then the conjugates were plasticized by glycerol and crosslinked by dialdehyde xanthan gum to fabricate active RosA-gelatin edible films. The results indicate that the RosA-gelatin edible films present good water resistance property, strong mechanical property and excellent ultraviolet light barrier ability. The conjugation of RosA confers gelatin-based edible films with effective antioxidant and antibacterial activities as expected. It is interesting that RosA-gelatin edible films after 3 months of storage still show good antibacterial activity as that of newly prepared ones, demonstrating the long-term antibacterial activity. Overall, the fabricated RosA-gelatin edible films may have promising application in the fields of food and pharmaceutical packaging.
危险品化学品经营许可证（带存储）