Chapter <233>: New techniques
USP General Chapter <233> Elemental Impurities—Procedures sets out the general conditions for testing, covering preparation,
analysis, and the parameters for validation. The preparation methods referred to above are neat, direct aqueous solution,
direct organic solution and indirect solution.
Neat samples are in such a state that they can be used without further preparation. More commonly used solutions will need
to be prepared prior to analysis, and the simplest of these procedures is preparation of a direct solution whereby a product
is dissolved or diluted with water/dilute acid or an organic solvent to give a solution for analysis.
In many cases, it may be desirable to treat the sample by breaking down any organic material contained within it; such a step
typically reduces the ffect of the matrix effect which might otherwise give rise to false positive/negative results. If a
sample is prepared in this way, then it is referred to as an indirect solution. These solutions are generally prepared using
a microwave digester. In this technique, a small amount of sample is weighed into a vessel and acid is added. The vessel is
sealed and placed into a microwave. In the microwave, the sample is heated to temperatures of up to 250 °C and pressures of
up to 55 bar. Under these conditions, the sample matrix is effectively destroyed and the metal atoms are released into solution.
After the sample is cooled, it is made up to a suitable volume with water ready for analysis.
ICP–MS and ICP–AES.
As noted above, Chapter <233> sets out two procedures for analysis, ICP–MS and ICP–AES. The latter is also sometimes referred
to as ICP–OES, which stands for optical emission spectrometry. In this technique, the sample solution is fed into an argon
plasma which has a temperature of approximately 10,000 °C. The sample matrix is destroyed under these conditions, and individual
atoms are released. These atoms are then excited to a higher energy state. As the excited atoms cool, they return to a "ground
state." The process releases energy in the form of light, the wavelength of which is specific to a particular element. When
this light falls on a detector, it can be quantitated and the amount of analyte can be evaluated.
ICP–MS is the second procedure specified in Chapter <223>. This technique also uses a plasma, but with this technique, the
plasma is used to ionize the metal atoms which are then fed into a quadrapole which separates the ions according to their
mass-to-charge ratio. Following separation, the ions fall onto a detector and the sample can be quantified.
Differentiating the new techniques.
Both ICP–AES and ICP–MS are able to analyze several elements simultaneously. As a result, sample throughput can be very quick,
typically 2–3 minutes per sample. Generally, it is fair to say that ICP–AES instrumentation is cheaper than ICP–MS, but both
instruments have relatively high running costs due to the consumption of argon in the plasma. The key difference between the
instruments is the detection limit. The ICP–MS typically has detection limits 100–10,000 times lower than that of ICP–AES.
Both techniques are capable of analyzing to the levels required by USP, but ICP–MS can offer a much lower detection limit.
Chapter <233> states that for both techniques, steps can be taken to remove matrix interferences. For ICP–AES, these interferences
can occur from overlapping wavelengths. In this case, alternative wavelengths can be used for analysis. Also, many instrument
manufacturers have correction techniques built into the operating software.
In the case of ICP–MS, the sources of matrix interferences come from the fact that different species can have the same mass/charge
ratio. For example, argon chloride appears at the same mass as arsenic, giving false positive results. To remove these interferences,
many instrument manufactures use special cells within the instrument that can add gases to the ions and mitigate the interferences.
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