Analysis of extractables and leachables in pharmaceutical preparations

Low density polyethylene (LDPE) is used as primary packaging material in ophthalmic preparations in the pharmaceutical industry. The 5 most likely impurities compounds from LDPE packaging material to pharmaceutical preparation of an ophthalmic preparation containing the active substance of cyclosporin were determined by detailed literature studies. The impurities identified were myristic acid, Irganox-1076, Irganox-1330, Irganox-1010 and Irgafos-168. For these impurities, tandem mass spectrometric ultra-fast high performance liquid chromatography method was developed and validated within the scope of extractables (EEAS) and leachables (SAS) studies. In the developed method, 220 nm ultraviolet detector wavelength and MRM mode mass detector were used. Isocratic elution was applied with BEH phenyl stationary phase and 0.1% ammonium formate solution, methanol (50:50, v/v) mobile phase system at a flow rate of 0.5 mL/min. Total analysis time is 2.4 minutes. The validation parameters of the developed method; limit of detection, limit of detection, linearity, accuracy, system precision, intra-day reproducibility, inter-day reproducibility, solution stability were performed separately for EEAS and SAS. Linear ranges of EEAS and SAS, respectively, Myristic acid; 0.2751-3.7425 µg/mL, Irganox-1076; 0.06694-3.8250 µg/mL, Irganox-1330; 0.0747-3.7350 µg/mL, Irganox-1010; 0.02818-3.7575 µg/mL and Irgafos-168; It is 0.02264-3.7725 µg/mL. Detection and quantification limits of EEAS and SAS was determined as, respectively, Myristic acid; 0.0834 µg/mL and 0.2751 µg/mL, Irganox-1076; 0.0223 µg/mL and 0.0669 µg/mL, Irganox-1330; 0.0234 µg/mL and 0.0747 µg/mL, Irganox-1010; 0.0088 µg/mL and 0.0282 µg/mL, Irgafos-168; 0.0078 µg/mL and 0.0226 µg/mL.