Critical Points in the Methodology of Preparing Copper (II) Histidinate Injections and their Quality Assessment Applying Color Measurement.

Copper (II) histidinate injection solution, applied in Menkes disease treatment, is characterized by low stability due to sensitivity to oxidation. The aim of this article was to determine the critical points of the injection preparation procedure, taking into account selection of appropriate packaging, determining the solution pH or application of an excess of L-histidine. In order to assess the stability of the Cu(His) complex, the spectrophotometric method (VIS: 400-800 nm), and the colorimetric method using a reflectance colorimeter were applied. The color changes observed using the CIELAB color system made it possible to determine: the differences in the observed color (ΔΕ) and the color chroma (C*) and hue (h°). It was found that the following parameters: λ and ΔE enable fast and objective assessment of copper (II) histidinate injection solution quality. The advantage of the colorimetric method is the non-invasiveness of the analysis which is performed through the packaging material (transparent vial). The developed methodology of preparing Cu(His) injections in hospitals or community pharmacies guarantees their stability for at least 6 months, provided that the solution is stored at lower temperatures (2-8°C or 4°C).