Identification of volatile extractables from plastic infusion bags and prediction their CYP enzymes inhibition potential by Silico methods

Abstract

• The volatile extractables from PVC infusion bag, non-PVC infusion bag and non-PVC infusion bottle were panoramically identified. • The new idea that high throughput potential toxicity prediction of extractables from drug packaging materials was introduce, and the potential toxicological properties of all the volatile extractables from the plastic infusion bags form the point of CYPs inhibition potential was predicted by using the ADME prediction platform. • The interaction forces between the potential toxic extractables and CYP enzymes revealed by using molecular docking method. In this work the volatile extractables from 3 kinds of plastic infusion bags, including polyvinyl chloride (PVC) infusion bag, non-PVC infusion bag and non-PVC infusion bottle, were identified by using gas chromatography-mass spectrometer (GC-MS) analysis, and the CYP enzymes (CYPs) inhibition potentials of the obtained extractables were predicted by using SwissADME prediction system. Meanwhile the interactions between the potential toxic extractables and CYPs were revealed by using molecular docking study. The GC-MS analysis results indicated that there were 40, 19 and 24 kinds of volatile extractables, including plasticizer, intermediate, stabilizer, lubricant, antioxidant, and impurity in antioxidants, identified from PVC infusion bag, non-PVC infusion bag and non-PVC infusion bottle, respectively. The SwissADME prediction indicated that 33 of extractables have CYPs inhibition potential. The molecular docking study indicated that stabilizer oleamide bind with 16 and 10 amino acid residues of CYP1A2 and CYP2C9, formed hydrogen and hydrophobic bonds; antioxidant 2,2′-Methylenebis (6‑tert‑butyl‑4-methylphenol) bind with 9 and 17 amino acid residues of CYP2C19 and CYP2D6, respectively, and formed hydrogen and hydrophobic bonds that may lead to the change of the conformation of CYPs and inhibit their enzyme activity. This work may provide new train of thought to predict the potential toxicological properties of the large amounts of extractables from plastic packaging materials.