Quantification of local zinc and tungsten deposits in bone with LA-ICP-MS using novel hydroxyapatite–collagen calibration standards

Abstract

Tungsten has recently emerged as a potential toxicant and is known to heterogeneously deposit in bone as reactive polytungstates. Zinc, which accumulates in regions of bone remodeling, also has a heterogenous distribution in bone. Determining the local concentrations of these metals will provide valuable information about their mechanisms of uptake and action. A series of bone (BN), 7 : 3 hydroxyapatite:collagen (HC), and hydroxyapatite (HA) standards were spiked with tungsten and zinc and used as calibration standards for laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis of bone tissue. The analytical performance of these standards was studied and validated at different step sizes using NIST SRM 1486 Bone Meal. The effect of matrix-matched calibration was assessed by comparing the calibration with BN and HC standards, which incorporate both inorganic and organic components of bone, to that of HA standards. HC standards were found to be more homogenous (RSD < 10%) and provide a linear calibration (R² > 0.994) with better accuracy compared to other standards. The limits of detection for HC at a 15 μm step size were determined to be 0.24 and 0.012 μg g⁻¹ for zinc and tungsten, respectively. Using this approach, we quantitatively measured zinc and tungsten deposits in the femoral bone of a mouse exposed to 15 μg mL⁻¹ tungsten for four weeks. Localized concentrations of zinc (942 μg g⁻¹) and tungsten (15.7 μg g⁻¹) at selected regions of enrichment were substantially higher than indicated by bulk measurements of these metals.