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.