USP 232 and ICH Q3D – Element Stability in ICP Standards

Regarding analytical methods, USP published General Chapter 233, which listed two appropriate inductively coupled plasma (ICP) techniques: optical emission (ICP-OES) and mass spectrometry (ICP-MS). No specific analytical methods are described in ICH Q3D. As ICP methods are common and widely applied, and since most routine ICP methods introduce samples in liquid form, this article will focus on solutions suitable for both ICP-OES and ICP-MS measurements.

When discussing element stability in ICP standards, three important considerations exist:

The matrix of the solution The concentrations of the elements Storage conditions (e.g., container material, temperature, etc.) For this discussion we’ll limit the definition of stable to encompass only chemical stability. An element is chemically stable in a particular matrix if it will remain at a specified concentration in solution indefinitely (i.e., hydrolysis, co-precipitation, adsorption/absorption, etc., will not occur). It is important to note, however, that the concentration of a chemically stable element can change with time due to physical processes, an example of which would be the loss of water vapor through transpiration (see www.inorganicventures.com/tct for more information). For storage conditions we’ll assume normal laboratory conditions (e.g., temperature) are present, but we’ll see that container material can have a significant impact when designing stable solutions. A last consideration is that an ICP solution may not require indefinite chemical stability; an element that is stable in a particular matrix long enough for daily ICP measurements may be suitable for the required purpose.

Solutions for ICP analyses typically use a dilute acid matrix to stabilize the elements of interest. The most common matrix is a dilute solution (1-10% by volume) of nitric acid (HNO3). This HNO3 solution may contain small amounts of complexing ligands such as fluoride or chloride which are useful for stabilizing some elements. The 24 elements listed in 232 and Q3D are compatible with a HNO3 matrix (Fig. 2), though safety and stability (both short and long term) are concerns for several elements. Osmium in the presence of oxidizing agents such HNO3 can form volatile and toxic OsO4. Other elements require fluoride (Sn, Sb) or chloride (e.g., Ru, Ir, Au) to promote long term stability in a HNO3 matrix. Mercury can exhibit instability in HNO3 when plastic labware is used due to Hg adsorption on plastic surfaces, though this effect is significant only at lower Hg concentrations (<100 ppm; see http://inorganicventures.com/guides-and-papers/mercury-chemical-stability for more information). If long term stability of Hg in HNO3 at relatively low concentrations is critical then preparation and storage in borosilicate glass is recommended.

Hydrochloric acid (HCl) as the solution matrix addresses most of the concerns associated with nitric acid, though chloride interferences are a concern for ICP-MS applications. All 24 elements are soluble in HCl (Fig. 3), though silver solubility is limited by both Ag and HCl concentrations. Low concentrations of Ag (≤10 ppm) are soluble in 10% (v/v) HCl, whereas higher concentrations of Ag (20-100 ppm) are soluble in 30-40% (v/v) HCl. Long term stability of silver in HCl is limited, however, by photoreduction of Ag-chloride to Ag0, and exposure to light should be limited (see http://inorganicventures.com/guides-and-papers/silver-chemical-stability for more information). One additional note regarding HCl matrices involves thallium, which must be present in solution as Tl+3 to avoid precipitation as Tl-chloride (similar to Ag). Commercially available Tl standards are frequently prepared from TlNO3 and are not stable when diluted in HCl.

It is therefore possible to create a safe and stable ICP standard that contains all 24 elements if HCl is the solution matrix.

If, however, HNO3 is the required matrix the following should be considered:

1. A pure HNO3 matrix is not recommended. Several elements will require complexing ligands such as F or Cl. However, as element concentrations decrease the required amount of additional matrix components such as HCl or hydrofluoric acid (HF) decreases as well.
2. The oxidation of Os to volatile and toxic OsO4 can occur in nitric acid and must be avoided. At dilute concentrations of ~2M or lower HNO3 is not a strong oxidizer (for more information visit http://www.inorganicventures.com/acid-digestions-inorganic-samples), and it is possible that OsO4 formation may be limited. However, we have not studied these effects in detail and mixing Os with any amount of HNO3 should be approached with caution.
3. The platinum group metals and Au are typically stabilized with HCl, to the extent that commercially available preparations frequently contain small amounts of Cl even if the solution matrix is HNO3. Mixtures of these elements with Ag or Tl+1 can create unstable chloride complexes. (To our knowledge Os is not available as a chloride-free standard.)
4. Mercury in HNO3 at low concentrations (<100 ppm) will suffer stability issues if plastic labware is used for preparation or storage. The U.S. Environmental Protection Agency has noted that the low concentrations of Hg found in environmental water samples can be stabilized in polyethylene containers using dilute HNO3 spiked with 1 ppm AuCl3. However, as Au is listed as an element of interest in Q3D this approach may not be suitable for all applications.
5. Elements such as Sn and Sb will require a complexing ligand such as fluoride to ensure stability in HNO3. In the case of fluoride it will be present as HF regardless of the fluoride source, and ICP sample introduction systems should be HF compatible. It is also possible to stabilize Sb using tartrate, and many commercially available Sb ICP standards use a combination of HNO3 and tartaric acid to stabilize Sb. However, if the application calls for the determination of both Sb and Hg, it should be noted that Hg will not be stable if mixed with a solution that contains tartrate. We therefore recommend a HNO3-HF matrix if Sn, Sb, and Hg analyses are required.

Summary

The 24 elements common to both USP 232 and ICH Q3D can be prepared in either a HNO3 or HCl matrix for ICP measurements, though the use of a HCl matrix significantly reduces safety and element stability concerns.

If an HCl matrix is acceptable then all 24 elements will be stable at 1-10 ppm in 10-20% (v/v) HCl when stored in polyethylene containers, though Ag will be photosensitive and exposure to light should be minimized. We recommend low-density polyethylene (LDPE) for solution preparation and storage due to its cleanliness, low cost, and availability (see http://inorganicventures.com/trace-analysis-guide/container-material-properties for more information).

If HNO3 is required, then trace amounts of HCl and HF are necessary. A 10 ppm solution of all 24 elements in 2-5% (v/v) HNO3 with trace HCl-HF and stored in LDPE would require monitoring for:

1. Osmium oxidation to OsO4. If OsO4 exists, false high results would be expected for ICP measurements as OsO4 volatility increases nebulization efficiency during sample introduction.
2. Silver, Au, and Hg instability. The stability of these elements is likely to be measured in hours to days. Note that redox reactions involving other PGM such as Pt may also occur and could result in instability for these elements as well.