Potential metal impurities in active pharmaceutical substances and finished medicinal products - A market surveillance study.

A market surveillance study has been established by using different atomic spectrometric methods for the determination of selected elemental impurities of particular interest, to gain an overview about the quality of presently marketed drug products and their bulk drug substances. The limit tests were carried out with respect to the existing EMA guideline on the specification limits for residuals of metal catalysts or metal reagents. Also attention was given to the future implementation of two new chapters of the United States Pharmacopoeia (USP) stating limit concentrations of elemental impurities. The methods used for determination of metal residues were inductively coupled plasma-mass spectrometry (ICP-MS), inductively coupled plasma-optical emission spectrometry (ICP-OES), and atomic absorption spectrometry technologies (GFAAS, CVAAS, HGAAS). This article presents the development and validation of the methods used for the determination of 21 selected metals in 113 samples from drug products and their active pharmaceutical ingredients.

Influence of dietary factors, age and nickel contact dermatitis on nickel excretion.

BACKGROUND: Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis. METHODS: We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods. RESULTS: A nickel detection limit of 0.2 µg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 µg/l (age 18-30 years) and 3.98 µg/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls. CONCLUSIONS: The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 µg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.