Laboratory Methods

While several analytical methods are available for trace element analysis and quantification, the overall best, in terms of accuracy, specificity, dynamic range, multielement capability, and precision, is ICP-MS. This technology, used in clinical laboratories since the 1980s, employs a very high temperature (~6000-10,000K) plasma to ionize a sample and mass spectrometry to detect specific isotopes. ICP-MS is, however, more expensive and technically difficult to perform than other techniques, and the possibility for interferences from isobaric, doubly charged, and polyatomic species exists. Interferences can be overcome by adjusting instrument settings and/or incorporating a collision or reaction cell (23,24).

AAS, analogous to spectrophotometry, is a common alternative method used for the detection of trace elements vaporized to gas-phase atoms in a flame or graphite furnace. The atoms absorb ultraviolet or visible light, leading to higher electronic energy levels. Each element absorbs a characteristic wavelength of light as the sample is passed through the flame or furnace, and the elemental concentration is determined from the amount of absorption. AAS has been replaced by ICP-MS in many laboratories because AAS generally measures only one element at a time whereas ICP-MS can be used to measure multiple elements simultaneously. ICP-MS can also accommodate a much wider dynamic range and is less subject to analytical interferences than AAS. An exception, however, is mercury, for which AAS performs very well and is widely used (25-27).

In order to facilitate population screening of blood lead, portability or field testing is desirable. As a result, anodic stripping voltametry, a technique that can be performed point-of-care using a capillary blood sample and a hand-held or small bench top device (LeadCare®), is commonly used. Briefly, lead in a blood lysate is plated onto an electrode. A stripping current is then applied to the electrode, the amount of which is directly proportional to the amount of lead in the sample. This method has shown excellent correlation with other methods such as AAS and ICP-MS for low concentrations of lead (28,29).

Serum iron concentrations are typically measured by releasing iron (Fe+3) from transferrin by acid and reaction of the iron to a chromogenic compound such as ferrozine following reduction to (Fe+2). In addition, the total iron binding capacity can be obtained by saturating the iron-binding sites on transferring with exogenous Fe+3 prior to analysis. Ferritin is another commonly used indicator and is typically measured by immunoassay (25,30). Elevated iron thought to be associated with chronic accumulation is confirmed and monitored with periodic liver biopsies for which quantitative iron concentrations can be determined by staining techniques and/or ICP-MS.

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