Optimised quality control method for determination of the radiochemical purity of [99mTc]Tc-mebrofenin and [99mTc]Tc-etifenin in a clinical context

ObjectivesIn the context of a supply disruption of mebrofenin (Cholediam)-based kits for radiolabelling with technetium-99m [Tc-99m], the medicine agencies allowed the importation of a back-up radiopharmaceutical diagnostic agent, etifenin (Techida), to ensure continuous management of patients with hepatobiliary disorders in nuclear medicine departments. There are still issues regarding the measurement of radiochemical purity (RCP) with these kits based on the European Pharmacopoeia and the Summary of Product Characteristics (SPC). This study aims to identify and to optimise, in a clinical context, the most suitable thin layer chromatography (TLC) method for the determination of the RCP in terms of speed of response and reliability for [Tc-99m]Tc-mebrofenin and [Tc-99m]Tc-etifenin. Methods[Tc-99m]Tc-etifenin (n=4) and [Tc-99m]Tc-mebrofenin (n=5) were individually controlled using six different TLC methods and one high-performance liquid chromatography (HPLC) method for impurity identification ([Tc-99m](TcO2)(n) and Na[Tc-99m]TcO4), RCP (%) and duration of analysis (min). Two TLC methods were selected according to the recommendations of the Pharmacopoeia and SPC, two others were exactly the same but with a heating step, and the other two corresponded to a mix between the methods of the SPC and the Pharmacopoeia that were chosen to optimise RCP determination parameters. ResultsRadio-HPLC analysis allowed effective separation of [Tc-99m]Tc-etifenin and [Tc-99m]Tc-mebrofenin with a retention time of 8.05 +/- 0.02 min and 8.94 +/- 0.07 min, respectively, from Na[Tc-99m]TcO4 (retention time 2.76 +/- 0.03 min). HPLC showed an absence of Na[Tc-99m]TcO4 for [Tc-99m]Tc-mebrofenin and 0.2% for [Tc-99m]Tc-etifenin. Among the TLC methods, we identified the most suitable method which ensures the most compliant RCP (98.3 +/- 0.9%) in a time of 31.5 +/- 1.1 min. Also, it allowed a time saving of 15 min compared with the methods proposed by the Pharmacopoeia and the SPCs. ConclusionWe propose a TLC method that accelerates quality control by an average of 15 min while guaranteeing a reliable RCP.