Measurement of ²²⁷Ac by Isotopic Ratio with ²²⁵Ac Using ICP-MS

A method is reported for the measurement of ²²⁷Ac using inductively coupled plasma mass spectrometry (ICP-MS) and isotope ratio analysis. The method has application for the quality testing of ²²⁵Ac produced as an active pharmaceutical ingredient (API). The ²²⁵Ac/²²⁷Ac isotope ratio is measured directly from ICP-MS count rate data and converted to an ²²⁵Ac/²²⁷Ac 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 ²²⁵Ac activity to obtain an absolute ²²⁷Ac activity. Thus, the method may be used to report the ²²⁷Ac content of an ²²⁵Ac 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 ²²⁵Ac and ²²⁷Ac. 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 ²²⁷Ac and 74-91% for 0.025 ng L^-1 of ²²⁷Ac. Intermediate precision was measured as 4.1% using replicate measurements (n = 12, two instruments) of ²²⁷Ac spiked samples (0.5 ng L^-1). The instrumental detection limits for ²²⁷Ac 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 ²²⁷Ac in ²²⁵Ac APIs. Actinium-225 samples are analyzed under this method without any need for ²²⁵Ac decay or ²²⁷Ac daughter in-growth. Sample preparation involves simple dilution of the ²²⁵Ac API in 3% HCl/1% HNO₃. The analysis takes as little as 2 h using equipment common to radioanalytical laboratories. Thus, the measurement of ²²⁷Ac by this method can be performed as part of routine ²²⁵Ac API quality testing and reported on release documents. This is a significant advantage over radiometric methods reported for the quantification of ²²⁷Ac in ²²⁵Ac APIs, which require days to weeks before reportable results can be obtained. The measurement of ²²⁷Ac by ICP-MS and isotope ratio analysis is rapid, accurate, and sensitive. The implementation of this method for ²²⁵Ac API quality testing will help ²²⁵Ac producers and end-users ensure product quality and demonstrate regulatory compliance.