Use of proton-induced X-ray emission (PIXE) analysis in the evaluation of large volume parenteral rubber stoppers

Abstract

The use of external beam proton-induced X-ray emission (PIXE) analysis for determining the elemental composition of three different types of rubber stoppers used to seal parenteral solutions is described. The stoppers were immersed in 0.9% sodium chloride solution in conical flasks. The flasks were then autoclaved in a pilot autoclave using an F o value of 15 min at 121°C. The PIXE measurements were performed at the 2.5 MeV Van de Graaff accelerator in the University of Helsinki. The results show that the PIXE method clearly revealed the differences between different types of rubber stoppers. The elements found were, e.g., Fe, Ti, Zn, Br. The limits of detection were 2 ppm for Ti, 6 ppm for Fe, 2 ppm for Cu, 1 ppm for Zn, 3 ppm for Br and 0.5 ppm for Pb. The concentrations of a certain element vary greatly from sample to sample, for example, that of Zn by a factor of 4000. The elemental compositions of 4482 PH 4001/45 and 4782 PH 4106/50 are nearly identical, whereas the elemental composition of 4443 PH 21/50 is more complicated. Heavy elements were either non-existent or present in very low quantities. PIXE analysis is useful for detecting and quantifying elements with atomic numbers greater than 12. A particular feature of the method is that many elements can be analyzed simultaneously if a detection system with sufficient resolution is available. The sensitivity of the method at the ppm level and the fact that analyses may be performed on samples of small size make it a promising technique for analyzing the chemical composition of rubber stoppers. This method could be used in various pharmaceutical applications, since analysis can be performed under a normal atmosphere without requiring the use of a vacuum.