Multivariate optimisation and validation of the analytical GC-FID for evaluating organic solvents in radiopharmaceutical

Abstract

ObjectiveAnalytical gas chromatography in line with a flame ionisation detector (GC-FID) method was developed and validated for evaluating organic solvents in radiopharmaceutical samples [18F]fluoro-ethyl-tyrosine ([18F]FET), [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluorothymidine ([18F]FLT). Variables of the carrier gas flow (mL min−1) and a split ratio of injection on the response of analysis time and resolution were optimised with the assistance of a two-level full factorial design and desirability function of Derringer. MethodsThe proposed procedure was validated following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guideline. ResultsExcellent linearity, R2 > 0.990 indicated that approximately 99% of the variance in the response could be predicted from ethanol and acetonitrile concentrations ranging from 0.8 to 7.5 mg mL−1 and 0.1 to 1.0 mg mL−1, respectively. The proposed procedure proved to be selective, sensitive and accurate (85 to 105%), with excellent repeatability and precision (relative standard deviation (RSD) < 2%). In assessing the robustness of the method, the proposed procedure also proved to be robust as the standardised effects values (SE) were insignificant (p > 0.05). ConclusionThe proposed method has also been successfully used for the quantitative determination of ethanol and acetonitrile in [18F]FET, [18F]FMISO and [18F]FLT samples. Analytes were well resolved (R, 7.9 – 8.1) within 3.5 min even though the column had a larger, 0.53 mm internal diameter. The proposed method is, therefore, relevant for routine organic solvent quality control analysis of any 18F-radiopharmaceutical derivatives.