Drug Discov Ther. 2021;15(5):227-235. (DOI: 10.5582/ddt.2021.01078)

Study of the compatibility of oral magnesium oxide preparations sold in Japan with the ICH-Q3D guideline for elemental impurities

Satoh M, Motokawa K, Uesawa Y, Ishikawa Y, Maeda H, Iida K, Tanaka H, Kosugi T, Nishizawa K


Magnesium oxide has been widely used as an antacid and constipation remedy. Currently in Japan, magnesium oxide preparations manufactured by five medical companies are marketed as prescribed generic drugs. In this study, we focused on metal elemental impurities present in 330 mg magnesium oxide tablets manufactured by each of these companies. The content of such impurities was determined by atomic absorption spectrometry and inductively coupled plasma mass spectrometry. We confirmed whether the content conformed to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, Guideline for Elemental Impurities (ICH-Q3D) based on the 30% control threshold. The content of these impurities varied among the five products (preparations A-E), but in all cases met the oral permitted daily exposure (PDE) criteria stipulated in ICH-Q3D. In 5 lots of preparation C and all lots of preparation D, the equivalent cadmium (Cd) intake for a daily maximum dosage of 2 g was higher than the 30% control threshold of 1.5 μg/day. By cluster analysis, preparations A-E were classified into preparations A + B and C + D + E and/or preparations A + B, C + D and E. The present study showed that all 5 preparations sold in Japan meet the PDE value standard of ICH-Q3D, and that preparations A and B meet the 30% control threshold. It is important that for preparations failing to meet the criteria, further improvements need to be sought, and impurities in magnesium oxide preparations need to be monitored to ensure their safety.

KEYWORDS: Magnesium oxide, metal impurity, ICH-Q3D, control threshold, cluster analysis

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