Laser ablation-inductively coupled plasmamass spectrometry has been used to generate elemental fingerprints of individual teeth, which have been sectioned to provide a sample which represents the time axis of tooth development. The ablated area is of the order of 100 µm across, and the ablation process is reproducible, measured using phosphorus. Studies on modern teeth reveal that the mercury and gold concentrations decrease from the outer (mouth exposed) part of the tooth to the inner newly deposited material. In contrast, the lead content increases from the outer part to the inner reflecting the exogenous origin of the mercury and gold, and the endogenous origin of the lead from the blood supply. Studies on a 19th century tooth from Spitzbergen reveal the presence of a range of lanthanide elements which occur naturally in the area. Studies of the concentrations of other elements present in teeth permit the comparison of data between teeth via the use of element/element ratios. The calcium/phosphorus ratio is recommended for this purpose.
This White Paper is focused on the technical aspects regarding quantifying pharmaceutically derived inorganic elements in biomatrices in support of GLP nonclinical and clinical studies using inductively coupled plasma (ICP) techniques. For decades ICP has been used in support of Environmental Protection Agency analyses and has more recently been applied for use in the pharmaceutical industry. Current bioanalytical method validation and sample analysis regulatory guidance applies to chromatographic platforms used for analysis of large- and small-molecule PK and TK assessments; however, it is not directly applicable to all aspects of various ICP techniques. Increasingly, quadrupole and high-resolution ICP-MS methods of analysis are being used to quantify inorganic elements contained in pharmaceutical compounds and biomatrices. Many elements occur endogenously in biomatrices, affecting quantification of blanks, standard curve samples, QC samples, and the selection of appropriate levels for the LLOQ.
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