A novel GC-MS method for rapid determination of headspace oxygen in vials of pharmaceutical formulations

A novel GC-MS method which requires small injection volumes was developed for fast and selective determination of headspace oxygen in pharmaceutical packages. This method does not require a specific GC column for separation of oxygen from other permanent gases such as nitrogen; instead it offers the advantage of using co-eluting nitrogen as the internal standard for quantifying oxygen in the headspace under electron ionization (EI, 70 eV) conditions. The relative ionization efficiency of oxygen to nitrogen, termed as ionization efficiency correction factor (IECF), can be measured using a control sample with known composition of oxygen and nitrogen such as the standard dry air used in this study. To avoid contamination, it is necessary to flush the syringe with pure helium. The measurements by the method are independent of the variations of sampling volumes. The determined headspace oxygen contents (R.S.D.<1%) in the containers of an investigational intravenous formulation using this method are consistent with the results obtained by an oxygen instrument at the manufacturing facility. The performance of the analytical approach was evaluated in the study of the container closure integrity at various storage conditions including upright and inverted orientations. The results suggest that there is no obvious oxygen penetration over 12 months. This method provides a convenient tool for measuring the levels of HS oxygen in vials of pharmaceutical formulations.