Validation of an HPLC method for assessing the chemical and radiochemical purity for in-house produced [18F]Sodium Fluoride radiopharmaceutical

Introduction: According to the current edition of the European Pharmacopoeia (Ph. Eur.), the High-Performance Liquid Chromatography (HPLC) method with a strong anion exchange column and both a UV/VIS detector and a radioactivity detector in series is recommended for assessing the chemical and radiochemical purity of [¹⁸F] Sodium Fluoride. Since fluoride and chloride ions lack absorbance in the UV/VIS range, developing an isocratic HPLC ion-exchange method that utilizes a conductivity detector with a suppressor, along with a radioactivity detector, could serve as an effective alternative to the method outlined in the Sodium Fluoride monograph(Ph. Eur. 01/2008:2100).
Methods: The method for assessing the chemical and radiochemical purity of [¹⁸F] Sodium Fluoride was developed and validated using a Dionex ICS 1600 chromatographic system. This system includes a radioactivity detector and a conductivity detector serially connected, along with a Dionex ADRS 6000 anionic suppressor. The analytical column used was a Dionex IonPac AS10, with a Dionex IonPac AG10 guard column. The mobile phase consisted of 0.1M NaOH, with a flow rate of 1 mL/min. [18F]Sodium fluoride was produced using the in-house method previously developed from our group1.
Results: In terms of specificity, the chromatograms obtained from the standard solution within the matrix (physiological solution) were examined and showed that the main peak can be distinguished from all the others. The resolution between fluoride and chloride peaks exceeded a threshold of 1.5. Reportable range was set from quantitation limit (QL) to 120 % of the upper specification acceptance criterion. The quantitation limit (QL) was established at 0.1356 µg/mL. Accuracy was demonstrated through recovery assessments of three spiked samples, which yielded values ranging from 97.74% to 106.16%. Precision was evaluated through repeatability tests, wherein the relative standard deviation (RSD) values of 0.425 for system precision and 0.145 for method precision fulfilled the criterion of RSD < 2%. The method's range is 0.1356 - 0.5424 µg/mL, and evaluations within this interval showed suitable accuracy, precision, and a correlation coefficient exceeding 0.99.