Validation of a cost-effective alternative for a radiochromatography method to be used in a developing country

Abstract

Introduction: The radiochemical purity (RCP) of technetium-99m labelled radiopharmaceuticals (RP) is important to ensure optimal scintigraphic image quality. In low-income settings, it may not be possible to use compendial analytical methods or expensive equipment for radiochemical purity analysis. All radiochemical analysis methods should however be validated against compendial or otherwise proven methods. To ensure the efficacy of RP prepared at Yaoundé General Hospital (YGH) Cameroon, this study cross-validated a cost-effective routine chromatographic method using a simple survey meter technique. A GMP-compliant method used at the University Medical Center Groningen (UMCG), the Netherlands was used as the comparator. Methods: Sestamibi, HMDP and DMSA kits currently used at YGH were reconstituted at UMCG with about 2000 MBq of freshly eluted sodium pertechnetate as described by the manufacturer, and spiked with eluate of the same generator to obtain a range of impurity concentrations. Samples of technetium-99m RP were spotted on 1 × 10 cm iTLC-SG strips and developed in appropriate mobile phases. Each strip was first scanned on the chromatogram-scanner used at the UMCG (standard method), and immediately thereafter the strip was cut in two pieces and radioactivity from each portion was counted with a small survey meter from YGH. The percentage RCP for each TLC strip was calculated using both counting methods. Internationally recommended validation parameters and acceptance criteria were used. Student’s paired t-test or ANOVA were used with ‘no significant difference’ designated at a 95% confidence-interval (P ≥ 0.05). Linearity of the survey meter was determined for Tc-99m. Readings obtained with the survey meter were also plotted against the scanner results. Results and discussion: The proposed method proved to be accurate (CV of mean RCP < 2), precise (RSD < 2%), linear (slope close to 1, r2 ≥ 0.99) within the RCP range of approximately 80% to 100%, and robust (P > 0.05). LOD and LOQ were determined for the survey meter. Specificity depends on chemical separation. As we were validating the suitability of a method to quantify radioactivity, specificity was not included in the validation parameters. Conclusion: The proposed method compared well with the standard method and is suitable as a reliable low cost method for limited resource settings.