Analysis of trace elements (Arsenic, Cadmium, Lead, and Mercury) in over-the-counter medicines from the United Kingdom, the Kingdom of Saudi Arabia, and India

Elemental impurities (EIs) in pharmaceuticals have become the subject of widespread interest. This is due to the implementation of new regulations by the United States Pharmacopoeia (USP <232>/<233>) and the International Council for Harmonisation (ICH Q3D) in 2018. These regulations mandate the monitoring of a wide range of elements, often present at low concentrations in pharmaceuticals. The aim of this study was to determine the concentrations of EIs (As, Cd, Pb, and Hg) in over-the-counter (OTC) medicines and evaluate possible human exposure to these trace elements, as well as to calculate and compare daily exposure values with the available USP <232>/<233> regulations. To do so, 38 common OTC medicines (paracetamol, cough, and ibuprofen/profen syrups) were collected from the United Kingdom (UK), the Kingdom of Saudi Arabia (KSA), and India. The samples were acid digested and then analysed using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). Weighted calibration curves and USP <232>/<233> ICH Q3D validation guidelines, including standard additions methodology, were used for analytical validation. The mean concentration of As, Cd, Pb, and Hg in OTC medicines were 4.73, 1.71, 15.40, and 2.03 µg/L, respectively. The results revealed acceptable levels of As, Cd, and Hg, but the samples had a relatively high amount of Pb compared to other trace elements in various medicine types from all countries. The data obtained from this study demonstrate that commonplace non-compliance with recommended daily dosages could readily result in exposures to Pb, reaching up to 50% of the Permitted Daily Exposure (PDE) limits for Pb in pharmaceutical products as defined by USP<232> (5 μg/day). When supplemented by exposures from other sources, this level of exposure has the potential to cause adverse health effects, particularly in young children. The use of a weighted calibration curve was shown to improve the accuracy of the analysis, particularly for concentrations close to method detection limits (DLs), whilst standard additions methodology was found to reduce matrix effects.