Metals and metalloids contamination in injectable hyaluronic acid dermal fillers: Multi-element evidence of market variability.

Injectable hyaluronic acid (HA) dermal fillers are widely used medical devices, yet data on their elemental impurity profiles remain limited despite the potential relevance of metals/metalloids to delayed inflammatory and hypersensitivity reactions. The aim of this study was to determine the multi-element impurity profiles of commercially available HA fillers and to evaluate whether product price category is associated with elemental content. Nineteen HA fillers were divided into low- (LP), mid- (MP), and premium-price (PP) groups and analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for 22 elements. Group differences (ANOVA/Tukey) and multivariate patterns (PCA, heatmaps, correlations) were used to compare impurity fingerprints across products. Several elements showed strong price-related gradients. Mean Al content decreased from 4200 mg kg-1 (LP) to 163 mg kg-1 (MP) and 41.8 mg kg-1 (PP), while As dropped from 10.1 to 0.426 and 0.01 mg kg-1, respectively. Sensitization-relevant, steel-associated Ni strongly discriminated groups (274 mg kg-1 in LP; 9.21 mg kg-1 in MP; <LOD in PP), and Cr decreased from 52.0 mg kg-1 (LP) to 15.1 mg kg-1 (MP) and 0.957 mg kg-1 (PP). Zinc also varied markedly (286, 49.9, and 20.2 mg kg-1 in LP, MP, and PP, respectively). However, some impurities were not monotonic with price: Mn and Co peaked in MP (109 and 17.8 mg kg-1, respectively), and Pb did not differ significantly across groups. Premium fillers formed the most compact cluster in PCA and generally exhibited lower, more homogeneous impurity fingerprints, yet price was not a universal proxy for purity at the element level. In the absence of harmonized injectable-filler-specific impurity thresholds, routine multi-element screening of HA fillers is warranted to support quality control and market surveillance.