Akademik Veri Yönetim Sistemi
Journal of Pharmaceutical Sciences, cilt.115, sa.2, 2026 (SCI-Expanded, Scopus)
Extractables and Leachables studies require highly reliable and sensitive analytical methods to ensure pharmaceutical product safety. Plastic additives are widely used during production to improve the physicochemical properties of polymeric products. However, these additives may constitute a potential toxicological risk by contaminating active pharmaceutical ingredients and pharmaceutical preparations. In this study, a short-term, sensitive, accurate, and reliable LC-MS/MS method was developed for the analysis of 15 plastic additives defined in the European Pharmacopoeia and validated in accordance with the ICH Q2(R2) guideline. An electrospray ionization source was used for the analyses in both negative and positive modes. Chromatographic separation was carried out using a reverse-phase phenyl C18 column and a mixture of methanol and ultrapure water containing 5 mM ammonium acetate as the mobile phase by the gradient elution method. As a result of method optimization, the flow rate and total analysis time were determined to be 0.7 mL/min and 15 min, respectively. Diphenyl phthalate was chosen as the internal standard. The LLOQ values of plastic additives were generally determined as 50 ng/mL (150 ng/mL for oleamide). The reliability of the method was verified by intraday/interday precision and accuracy analyses. Both extractable and leachable studies were performed using the developed method. It was effectively used to detect plastic additive contamination in pharmaceutical products such as bromobutyl stoppers, LDPE containers, disposable eye drop packaging, and polypropylene bags. The developed LC-MS/MS method was successfully applied to the analysis of pharmaceutical formulations containing 1.4% polyvinyl alcohol and 0.6% povidone, sodium hyaluronate, salbutamol sulfate, and 0.9% isotonic sodium chloride.