Development and validation of a gamma spectrometry method for actinium-225 quantification and routine radionuclidic purity monitoring.

Abstract

The development and validation of analytical methods are critical to ensure the quality, safety, and efficacy of radiopharmaceutical products. This study describes the development and comprehensive validation of a simple, accurate, and reproducible analytical method for the quantitative determination of ²²⁵Ac radionuclidic purity using high-purity germanium gamma spectrometry. Validation was performed according to ICH Q2/EANM guidelines and assessed key performance characteristics, including specificity, accuracy, precision, repeatability, linearity, minimum detectable activity/limit of quantification, and range. The method demonstrated excellent specificity, as sufficient resolution was achieved to distinguish gamma emissions relevant to potential impurities in ²²⁵Ac samples. Linearity was established over the activity range of 1.55-3060 Bq, yielding a correlation coefficient greater than 0.99. Accuracy studies showed mean recovery values within 98.2 ± 2.4%, confirming the method's trueness. Precision was evaluated through intra-day and inter-day studies, with ANOVA confirming no statistically significant inter-day variability, and produced relative standard deviation values below 5%, indicating acceptable repeatability and intermediate precision. The minimum detectable activity and limit of quantification were determined to be 0.64 Bq and 1.55 Bq, respectively, demonstrating sufficient sensitivity for routine analysis of ²²⁵Ac. However, it should be noted that detection sensitivity for long-lived contaminants (e.g., ²²⁷Ac and ²²⁹Th) is limited by their low gamma emission intensities and may require delayed measurement or complementary analytical techniques for definitive quantification at low activity levels. Nevertheless, the results of the method-development and validation work support its application to the analysis of ²²⁵Ac radiopharmaceuticals and confirm its appropriateness as a routine assay for periodic radionuclidic-purity assessment.