<p>This study was intended to assess the concentration of 15 elemental impurities and associated health risks in 38 samples of active pharmaceutical ingredients (APIs) collected from different Jordanian pharmaceutical manufacturers using inductively coupled plasma mass spectrometry (ICP-MS). The concentrations of the targeted elemental impurities were within or below the permissible limits except for ²⁰⁸Pb as recommended by the United States Pharmacopeia (USP – NF 2022) and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use ICH Q3D (R2). The hazard index (HI) of elemental impurities was less than 1 as established by the United States Environmental Protection Agency (US EPA) in all tested API samples except Amoxicillin. Validation parameters performed in this study showed a good accuracy and validity of the ICP-MS analysis method, with a good linearity (R² ˃ 0.996) for all elemental impurities, instrumental LODs varying between 0.001 × 10^− 3 µg. mL^− 1 for ²³²Th and 6.209 × 10^− 3 µg. mL^− 1 for ²⁰⁸Pb, and recovery ˃ 95%. Analysis of variance (ANOVA - one way) was used to compare the means of ten categories of medication groups for 15 targeted elemental impurities. The results show that all elemental impurities have p-values &gt; 0.05 except for ⁶⁰Ni (0.018), and ²⁰⁹Bi (0.021). This study investigated several elements that have been rarely reported in previous studies and further integrated elemental profiling with health risk assessment, hence providing new insights and adding novel data to the current body of scientific knowledge.</p> Graphical Abstract <p></p>