Procedure Validation of Elemental Impurities and Observation in Crude Drugs and Kampo Extracts

The General Tests 〈2.66〉 Elemental Impurities section was newly included in the 18th edition of the Japanese Pharmacopoeia to support the transition from the conventional simultaneous control of elements in drug products via colorimetric methods to the individual control of elemental impurities via instrumental analyses. This shift enables a more appropriate form of control that considers the toxicological risks of each element. Although the control method outlined in 〈2.66〉 does not apply to crude drugs, we herein investigated its applicability to crude drugs and Kampo Extracts to understand the risks of elemental impurities further. Based on the principles in 〈2.66〉, the quantities of seven elements [cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg), cobalt (Co), vanadium (V), and nickel (Ni)]-classified as Class 1 and 2A elemental impurities that require a thorough risk assessment-were measured. Ten crude drugs, whose medicinal parts are roots and rhizomes (which are more likely than other parts to accumulate elements from the soil), and twelve Kampo Extracts containing these crude drugs were tested via validation of the analytical methods. We consider that the procedures of Elemental Impurities described in 〈2.66〉 can be applied to the herbal medicines and Kampo Extracts examined in this study. However, considering the administration route of crude drugs and their products, controlling the elemental concentrations as per the permitted concentrations is challenging; instead, the elements should be controlled individually in Official Monographs considering actual measured contents.