Results
Figure 1: Inductively coupled plasma–optical emission spectrometry spike recoveries of test samples (with sample matrix) at
various concentrations of the control limits. Acceptance criteria are 80–150%. (ALL FIGURES ARE COURTESY OF THE AUTHOR)
|
For ICP–OES, the results of the accuracy tests, in which a blank sample and a matrix sample (see Figure 1) were spiked with
the elements of interest, showed that the spike recoveries were within the limits set by <233> (i.e., 80–150% of the spiked
values). The six repeatability samples and intermediate precision (i.e., reproducibility) gave relative standard deviation
(RSD) values of less than 3% and 16%, respectively, for all analytes. The results of the sample analysis (see Table I) revealed
that all of the elements, with the exception of arsenic, were below the component limit. The level of arsenic exceeded the
component limit by 100%, and if the maximum daily dose of the product were taken, the PDE would be exceeded by 300%.
Table I: Results of the inductively coupled plasma–optical emission spectrometry sample analysis with instrument and method
detection limits.
|
The ICP–MS results demonstrated that most pharmaceuticals displayed elemental concentrations well below the specified limits.
Figure 2 shows data for four of the medicines that had, in general, higher concentrations. All elements of interest were below
the component limit in drugs A to D. Chromium and manganese were above the component limits in drug B, and although drug C
did not exceed any of the USP limits, it contained a high level (i.e., 8 mg/g) of aluminum. Spike recoveries to determine the accuracy of the method fell
within the acceptance criteria, even for a spike of 0.5 μg/g for all elements (except mercury at 0.01 μg/g).
Conclusion
ICP–OES and ICP–MS are recognized by USP as the preferred techniques for the analysis of trace elemental impurities in pharmaceutical
products, in compliance with the requirements of the proposed USP <232> and <233>. The multielement analysis capabilities of ICP–OES and ICP–MS make them excellent tools for processing multiple
analytes in large numbers of samples quickly and efficiently. The methods offer superior performance with simple sample preparation,
fast analysis times, and superior sensitivity, compared with complex and less efficient sulfide precipitation-based detection
methods. Overall, the methods offer exceptional robustness, performance, and accuracy, while improving productivity for multi-elemental
measurements in complex matrices.
Matthew Cassap is a senior applications specialist at Thermo Fisher Scientific, 19 Mercers Row, Cambridge, UK, tel. + 44 1223 347 417, matthew.cassap@thermofisher.com
.
References
1. USP, "USP Heavy Metals Testing Methodologies Workshop" (Rockville, MD, 2008),
http://www.usp.org/pdf/EN/hottopics/2008-MetalsWorkshopSummary.pdf, accessed Sept. 30, 2011.
2. USP, "Hot Topics: Elemental Impurities" (USP, Rockville, MD, 2011),
http://www.usp.org/hottopics/metals.html, accessed Sept. 30, 2011.
|
