COMPLEX PHARMACEUTICAL MATRICES continued
(Waltham, MA) ELAN DRC II ICP-MS system was used to measure the concentrations of the se- lected elements. As internal standards, 45Sc, 89Y, 115In, and 159Tb were used.
Analytical procedure Whole tablets ranging in mass from ca. 400
to 700 mg were placed into the sample pellet holder and the microwave-induced oxygen combustion (MIC)/digestion procedure was performed. Three replicates of each tablet were repeated.
The sample holders were mounted with samples and positioned in the quartz diges- tion vessels (Figure 2). Six milliliters of 20% (v/v) diluted HNO3
solution was pipetted
into each quartz vessel, closed, and loaded into the Rotor 8N. After placing the rotor into the Multiwave PRO microwave reaction system, the vessels were pressurized with 20
bar of high-purity oxygen. With microwave irradiation applied, the samples were ignited, reaching temperatures of approx. 1000 °C. This MIC application enabled total and complete mineralization. Digestion blanks and calibra- tion verification standards were processed with every MIC digestion.
The microwave method had a total processing time of approx. 45 min (including heating and cooling). The digestion solutions were all clear, with a residual carbon content of <1%, highlight- ing the efficacy of the combustion/digestion technique.
Evaluation: MIC procedure The microwave-induced oxygen combustion
method was evaluated by spiking the absorbing solution prior to digestion with each element in a magnitude equal to 1 and 10 μg/g for the solid samples. Any losses of elements during the digestion would be critical for evaluation and validation of the digestion method against the conventional USP procedures. Table 1 shows the recovery data of the MIC procedure in % for Aspirin A.
Table 1 – Validation of the digestion efficiency of the MIC procedure*
The four Class 1 elements (As, Cd, Hg, and Pb) marked in gray showed recoveries between 96% and 102% for both spike levels. The recoveries for the Class 2 elements, with the exception of os- mium, ranged from 86% to 112%. The high value of osmium can be explained as the formation of volatile osmium tetroxide (in the oxidative nitric acid digestion medium) causing false high readings. A longer nebulization time, or the use of hydrochloric acid for osmium analysis, elimi- nates these false high readings.
Evaluation: ICP-MS procedure Incomplete digestion of samples can lead to
matrix effects, reducing the accuracy of mea- surement methods. To examine matrix effects, sample solutions were spiked postdigestion at 10- and 100-μg/L levels representing concentra- tions in the tablets at 1 and 10 μg/g.
The results in Table 2 demonstrate excellent recoveries for almost all elements of interest, at both low and high spike levels. This suggests a minimized matrix effect due to near-complete mineralization during the combustion and di- gestion procedure.
Table 2 – (Confirmation of) complete sample mineralization via MIC procedure*
Figure 2 – MIC vessel cross-section: Simultaneous ashing/combustion and acid digestion.
*Spike recovery data (%) for USP <232> ele- ments; samples spiked at two concentration levels prior to MIC digestion procedure.
AMERICAN LABORATORY • 24 • JUNE/JULY 2013
*Postdigestion spike recovery data (%) for USP <232> elements at high and low concentration levels; no matrix interferences during ICP-MS analysis.
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