Universally Applicable Methods for Comprehensive Risk Assessment of Elemental Impurities in Vitamin A and D Preparations

Title:Universally Applicable Methods for Comprehensive Risk Assessment of Elemental Impurities in Vitamin A and D Preparations

Volume: 20 Issue: 8

Author(s): Zhang Qiao, Shen Mengmeng, Zhu Li, Xiao Chaoqiang*, He Shuwang and Yang Jie*

Affiliation:

• Shandong Dyne Marine Organism Pharmaceutical Co., Ltd., Weihai, 264300, P.R. China

• Shandong Dyne Marine Organism Pharmaceutical Co., Ltd., Weihai, 264300, P.R. China

Keywords: Vitamin, children, heavy metal contamination, ICP-MS, digestion method, elemental impurity.

Abstract:

Background: Vitamin A and D deficiency in children is a common public health problem. In China, almost all children are administered vitamin A and D preparations daily and they should be consumed continuously until the age of 18. Children are sensitive to elemental impurities, including heavy metals. However, there are no regulatory requirements or reports on the risk assessment of elemental impurities in marketed vitamin A and D preparations.

Objective: The aim of this study was to propose an accurate and efficient method suitable for samples from different manufacturers to detect elemental impurities and conduct risk assessments according to the ICH Q3D guidelines.

Methods: We developed a universally applicable digestion method for capsules and an ICP–MS method for quantitative analysis of 28 elemental impurities in vitamin A and D formulations. These methods were validated according to the USP 233 guidelines. Elemental impurities in 15 batches of vitamin A and D products from 10 manufacturers and their capsule shells were determined, and risk assessment was conducted according to the International Council for Harmonization Q3D guidelines.

Results: All elemental impurities of toxicological concern met the Q3D requirements. However, the concentrations of various elements, including those of lead (not detected to 4.1 µg/g), arsenic (not detected to 7 µg/g), aluminum (not detected to 888 µg/g), and palladium (not detected to 36 µg/g), varied markedly. Moreover, the lead content in one batch from one manufacturer exceeded the control threshold.

Conclusion: In this study, we successfully developed an effective digestion method for processing capsules containing samples from different sources and a sensitive ICP–MS method for quantitative determination of 28 elemental impurities in vitamin A and D preparations. ICP–MS should be implemented for the evaluation and control of elemental impurities in vitamin A and D preparations. This will ensure safe long-term vitamin A and D supplementation in children.

Cite this article as:

Qiao Zhang, Mengmeng Shen, Li Zhu, Chaoqiang Xiao*, Shuwang He and Jie Yang*, Universally Applicable Methods for Comprehensive Risk Assessment of Elemental Impurities in Vitamin A and D Preparations, Current Pharmaceutical Analysis 2024; 20 (8) . https://dx.doi.org/10.2174/0115734129317487240906073916