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Traces in Solution Cost-Efficient Trace Metal Analysis with Gravimetric Solution Preparation

Editor: Ahlam Rais

Most of the chemical elements in a sample can be determined using two analytical techniques: ICP-MS and ICP-OES — as long as they are in solution. Most samples, however, are solid and must be dissolved before they can be analyzed. Here, gravimetry can provide valuable services.

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Schematic of ICP-MS setup.
Schematic of ICP-MS setup.
(Source: Mettler Toledo)

Accurate preparation of samples and standards is the most time-consuming part of any analysis in the laboratory. It starts to become crucial when the concentrations are as low as 0.001 μg/g, as is the case with standard solutions for inductively coupled plasma (ICP) analysis. Manual preparation is prone to a multitude of risks. One is errors in stock solution preparation during the weighing of a specific amount of a standard. Other errors can occur during the multiple dilution stages. With automated dispensing, the solution is prepared gravimetrically. This helps to avoid variability in weighing, by reducing the effect of environmental influences and different operators. It also eliminates human error in calculations or recording and transcribing data. Saving time in sample and standard preparation, and reducing the number of standards and solvents used, minimizes the cost of the entire analysis.

ICP-MS (inductively coupled plasma mass spectrometry) and ICP-OES (inductively coupled plasma optical emission spectrometry), also known as ICP-AES (inductively coupled plasma atomic emission spectro­metry), are analytical techniques that enable the detection of most chemical elements (in solution). Both ICP-MS and ICP-OES have become essential tools in meeting the new requirements for the USP General Chapters 232/233 on elemental impurity analysis.

The characteristics that make ICP-MS unique are its high sensitivity, wide linear dynamic detection range, and the high specificity that is required for accurate detection and quantification. ICP-MS has superseded AAS (atomic absorption spectroscopy) in many laboratories, despite the older technique’s good sensitivity for most metals and freedom from interference.

A typical ICP-MS or ICP-OES sample is a solid which needs to be dissolved in an appropriate medium before analysis. In the case of metals, which are insoluble in water and organic solvents, acid digestion is used, if necessary with a combination of acids at elevated temperatures. Nitric acid oxidizes metals to soluble nitrates, and these solutions are then analyzed using ICP.

Wide-ranging Applications

ICP-MS is an important analytical technique that can be applied to trace analysis in environmental, industrial and forensic samples, as well as quality control of medical, biological, pharmaceutical, and petrochemical samples. It is also widely used in water quality control, and for the identification of contaminants in the food and beverage industry. It allows, for example, the assessment of water quality and of sulfur-containing fuels. ICP-MS is important for the detection of heavy metals (such as arsenic, cadmium, lead, and tin) in food. High levels of arsenic (As) can be found in contaminated fish, and cadmium (Cd) in soil, due to the use of insecticides, fungicides, and fertilizers. Heavy metals can be toxic for humans, when not metabolized by the body, as they accumulate in the soft tissues. ICP-MS can be coupled with different separation techniques, and hence has become the most versatile tool for elemental quantification.

New legislation requires more sensitive methods, even pg/L (picogram per liter) levels of newly emerging contaminants. For example, quantification of proteins presents one of the most challenging tasks. All metal and metalloid species within a cell or tissue type represent one of the most dynamic research areas that developed from element specification. The use of ICP-MS during drug development and quality control in pharmaceuticals, especially quantitative analysis of the drug, its metabolites and impurities, represents a further application field. Chlorine, bromine, and iodine, which are essential parts of many drugs, also facilitate measurement by ICP-MS.

Additional Information
How ICP works

The principle of ICP (inductively coupled plasma) techniques is as follows: the sample (in solution) is pumped through a nebulizer into a spray chamber. The aerosol produced by this process is introduced into a plasma generated at the end of a quartz torch by a cooled induction coil through which a high- frequency alternating current flows. The plasma is extremely hot: 6000-7000 K, or up to 10,000 K in the induction zone. This inductively coupled plasma has sufficient energy to ionize the sample atoms, allowing simultaneous analysis of about 60 elements. In ICP-OES (optical emission spectrometry), the excited atoms and ions emit radiation at specific wavelengths. Each element has a characteristic emission spectrum. The light intensity is measured with a spectrophotometer, and can be converted into a concentration using calibration measurements. In ICP-MS, a mass spectrometer (MS) separates and quantifies the ions using electron multipliers, which convert ion currents into electrical signals. The magnitude of each signal is proportional to the number of analyte ions present in the sample. The signal intensities of each species are measured and converted into concentrations.

Advantages of ICP Techniques

The greatest advantage of ICP-MS is its extremely low detection limits compared to other analytical techniques. It also has a large linear range. It is suitable for the detection of the largest number of elements (82). It can distinguish between isotopes. However, it is an expensive technique.

ICP-AES (or ICP-OES) is a lower-cost alternative (2-3 times cheaper than ICP-MS) and has the capacity for high throughput. It is suitable for the detection of most elements (73). It can efficiently measure between 1 and 60 elements per minute.

Quantitative Determination

The lower range of application depends on the matrix in use. For most elements this is between 0.001 μg/g (1 ng/g) and 0.1 μg/g. Quantitative determination is based on calibration with a standard solution, as there is a linear relation between the intensity of the ion signal and the concentration of the element. Single- and multi-element standard solutions are commercially available in concentrations of 1000 mg/l. The shelf life of diluted element solution (1–10 μg/l) is limited and it should be freshly prepared at least every three months. If low concentrations are needed, these have to be prepared each day. 0.5 ml/l nitric acid is used as a chemical blank solution. For each element, one calibration line with at least four concentrations should be prepared, and one reagent blank solution is measured in each case as well. At least three measurements are performed automatically and averaged. Working standards are in the range of around 10 μg/mL.

Producing Standard Solutions

Mettler Toledo is changing the way these standard solutions are prepared. The XPR Automatic Balance can dispense solids and liquids directly into vials, so that standard solutions can be prepared more efficiently and cross-contamination can be reduced. As the solids are already weighed, it makes sense to also add the solvent gravimetrically, to achieve the best accuracy. The liquid dispensing automatically compensates for under- or overshoot in powder weight, as the amount required is calculated from the desired concentration. Consumption of standard and solvent can be reduced, as smaller amounts can be weighed whilst still adhering to the USP regulations (0.1 mg/g in one step).

In addition, it is not necessary to round up the volume to the nearest volumetric flask size. This is important as the price of standards can vary between 60–1180 dollars per g, and standard target weights are between 3–250 mg. The gravimetric approach allows you to weigh exactly the amount you need. This is perfect for the preparation of stock solutions and dilution. With the new automatic system containing an upgraded liquid dosing head, it is now possible to dispense diluted acids. As there are no metal parts in the dosing head that would come into contact with the solvent, no elements are washed out that would disturb the analysis.

Furthermore, according to the standards, glass or polyvinyl chloride (PVC) should not be used for the determination of elements at very low concentrations. Instead, it is recommended to use perfluoroalkoxy (PFA), fluorinated ethylene propylene (FEP) or quartz containers, cleaned with hot, concentrated nitric acid in a closed system. For a higher concentration range, high-density polyethylene (HDPE) and polytetrafluoroethylene (PTFE) containers are allowed for sample collection. All these requirements are met in the Mettler solution. By connecting the XPR Automatic Balance to LabX software, all weighing data and related process information can be handled automatically. LabX provides user guidance directly on the balance terminal and saves all information in a secure centralized database, ensuring full trace­ability and data integrity. In additi­on, all tasks, users, and instruments can be managed centrally. LabX is easily integrated with the laboratory information management system (LIMS), allowing bi-directional data transfer. LabX enables laboratories to take a big step towards digitalization and guarantees seamless data flow throughout the entire analysis.

Gravimetric dosing is an accepted method of weighing, as referenced in USP <1251> Weighing on the Analytical Balance. In addition, USP <841> Specific Gravity supports the preparation of solutions gravimetrically. The gravimetric method requires a concentration conversion from mg/ml to mg/g, but revalidation of SOPs is not needed.

* Contact: Mettler-Toledo, 35396 Giessen/Germany Phone: +49 641 507-444