ICP-MS as a Diagnostic Tool

Stable, Maintenance-Free Operation

HP 4500 ICP-MS is a perfect tool for the analysis of clinical samples, including whole blood, hair, serum, and urine.

• A programmable peristaltic pump system allows for selection of the optimum rinse time to help ensure both large sample throughput and a reduction of the carry-over effects. The system design allows stable, maintenance-free operation for up to one week, with a 12-hour-per-day usage.

• The software offers easy access to the electronic sample log, simplifying the bookkeeping and billing of the customers. Specific QA/QC protocols can be created and automatically executed by modifying existing QC software. The software allows for the definition of QA/QC goals and formalization of pass/fail criteria, and offers multiple choices of action upon failure.

• Superior detection limits allow the dilution of whole blood, serum, urine, and other clinical samples by a factor of 20 or 50. High dilution factors benefit the analysis two-fold. First, by practically eliminating the need for the matrix-matching of standards and allowing the use of the same aqueous calibration standards for multiple sample kinds. Second, by reducing the presence of unwanted species in the sample, simplifying the data interpretation, and reducing instrument maintenance requirements.

• Unattended analysis of completely unknown samples is possible, even with unusually high levels of some analytes. User-friendly software assists in the development of the acquisition method. The custom report/database generator allows fast data reporting in any format. Data can also be transferred electronically and networked.

"Essential" Versus "Toxic" Elements

An element is considered essential if it meets two criteria:

1. Its absence from the diet causes departures from normal growth and metabolism and the development of pathological symptoms.
2. Pathological symptoms can be relieved by returning the element to the diet.

In extreme deficiency, death results. Many elements can cause a toxic response if present in excess; some even a mortal toxic response. Because of this dual behavior, it is sometimes difficult to classify an element as "essential" or "toxic".

The following elements are classified as highly toxic: arsenic, cadmium, lead, and mercury. Aluminum, antimony, barium, beryllium, bismuth, lithium, nickel, strontium and thallium are usually considered potentially toxic or neutral. Chromium, cobalt, copper, iron, magnesium, manganese, nickel, selenium, and zinc are considered to be essential.

The Case of Mercury

A major clinical application of the HP 4500 ICP-MS system is the determination of mercury in whole-blood samples. Mercury is a toxic element for humans and animals. It is toxic in any of its three forms: elemental, inorganic, and organic. Mercury can cause hyperactivity, mental and emotional changes, neuromuscular disorders, and loss of appetite. Even very low levels of mercury have been found to supress biological selenium activity.

Inorganic mercury is a renal toxin. The measurement of whole-blood mercury (mostly in its organic form) is an indication of recent exposure; however, it does not correlate with mercury levels in the brain. Organic mercury is found in wood preservatives, paints, fungicides, cosmetics, foods, and seeds. Urine mercury is used for the evaluation of inorganic forms.

Elemental mercury is used in thermometers, some batteries, and dental amalgams. Mercuric salts are found in caramel, topically applied medicines, plastics, and some foods. Mercury poisoning was common in 18th-century Europe when mercury was used to make felt for the then popular top hat. The hat makers displayed behavioral changes typical of those resulting from mercury exposure.

Multielemental Analysis in 3 Minutes

Figure 1 shows an example of a calibration curve for the determination of mercury in 20-fold diluted clinical samples. Mercury can be determined in clinical samples either in a single-element determination or simultaneously with other elements. The analysis time per sample is about three minutes for multielemental analysis, and about one minute for single-element determination.

Two types of sample preparation procedures for whole-blood and serum samples are customarily performed: dilution with nitric acid and two-step dilution with tetramethylammonium hydroxide (TMAH).¹ The latter method can be considered a room-temperature digestion, followed by a dilution with distilled deionized water. Dilution factors of 20-fold and 50-fold are used most frequently. The HP 4500 is fitted with either concentric (Meinhard Type C) or Babington nebulizer and an ASX-500 autosampler (CETAC Technologies, Inc., Omaha, NE).

An example of operating parameters for both routine quantitative analysis and semiquantitative analysis is shown in Table I. The samples were analyzed in unattended mode. Analysis of whole blood is usually requested for heavy metals: arsenic, cadmium, lead, and mercury. Table II presents the results of an analysis of certified whole-blood samples.

Screening the Samples

Semiquantitative analysis is a very powerful tool in sample screening. It provides qualitative information about over 70 elements in a time equal to a single-element determination by some other analytical methods (atomic absorption). Quantitation with an accuracy of +/- 10% can be achieved.

The semiquantitative spectrum of the whole-blood sample is shown in Figure 2. The sample was only certified for lead concentration (170-240 ng/mL), and the value determined during semiquantitative analysis was 170 ng/mL. The sample was prepared using TMAH dilution. The semiquantitative spectrum of the blank (0.1% TMAH) is shown in Figure 3. Semiquantitative analysis was proven to be useful in the discovery of some sample matrix behavior exhibited exclusively by clinical samples.²

1. Bakowska, E. and Hedrick, J. L. Paper No. 012, FACSS XXIII, Kansas City, MO (1996).
2. Nixon, D. E. at al. Paper No. 013, FACSS XXIII, Kansas City, MO (1996).