Abstract
A method is reported for the measurement of (227)Ac using inductively coupled plasma mass spectrometry (ICP-MS) and isotope ratio analysis. The method has application for the quality testing of (225)Ac produced as an active pharmaceutical ingredient (API). The (225)Ac/(227)Ac isotope ratio is measured directly from ICP-MS count rate data and converted to an (225)Ac/(227)Ac activity ratio by using basic nuclear decay equations. The activity ratio, which is itself a measure of radioisotopic purity, is coupled with an orthogonal measurement of (225)Ac activity to obtain an absolute (227)Ac activity. Thus, the method may be used to report the (227)Ac content of an (225)Ac API in absolute or relative terms. The methodology was evaluated against appropriate validation criteria (e.g., linearity, accuracy, precision, specificity) by analyzing a series of solutions containing known quantities of (225)Ac and (227)Ac. Accuracy was evaluated using a spike recovery study. The spike recoveries were 100-108% for samples with 0.100 to 2.00 ng L(-1) of (227)Ac and 74-91% for 0.025 ng L(-1) of (227)Ac. Intermediate precision was measured as 4.1% using replicate measurements (n = 12, two instruments) of (227)Ac spiked samples (0.5 ng L(-1)). The instrumental detection limits for (227)Ac were shown to be as low as 23 Bq L(-1) (0.0086 ng L(-1)), which is lower than comparable methods for the quantification of (227)Ac in (225)Ac APIs. Actinium-225 samples are analyzed under this method without any need for (225)Ac decay or (227)Ac daughter in-growth. Sample preparation involves simple dilution of the (225)Ac API in 3% HCl/1% HNO(3). The analysis takes as little as 2 h using equipment common to radioanalytical laboratories. Thus, the measurement of (227)Ac by this method can be performed as part of routine (225)Ac API quality testing and reported on release documents. This is a significant advantage over radiometric methods reported for the quantification of (227)Ac in (225)Ac APIs, which require days to weeks before reportable results can be obtained. The measurement of (227)Ac by ICP-MS and isotope ratio analysis is rapid, accurate, and sensitive. The implementation of this method for (225)Ac API quality testing will help (225)Ac producers and end-users ensure product quality and demonstrate regulatory compliance.