Multivariate optimization and validation of a procedure to direct determine acetonitrile and ethanol in radiopharmaceuticals by GC-FID

Abstract

A fast and simplified analytical procedure was developed and validated for the direct determination of organic solvents (acetonitrile and ethanol) in radiopharmaceuticals samples ([18F]FMISO, [18F]FES and [18F]FLT) by gas chromatography coupled with flame ionization detection (GC-FID). Optimization studies were performed with the aid of two-level full factorial design. The optimum conditions were located using Derringer's desirability function. Procedure validation assured the compliance of the assay to Brazilian regulatory agencies standards (ANVISA and INMETRO). Values for LOD and LOQ were commensurate with the level at which the impurities must be controlled. Good linearity was achieved (R ≥ 0.990) for acetonitrile and ethanol concentrations ranging from 0.003 to 0.09% (w/v) and 2.1 to 11.0% (v/v), respectively. Accuracy and precision assessments were performed using samples fortified with standards (spiked samples). The developed procedure proved to be selective, sensitive, accurate (95.9–117.8% of nominal values) and precise (RSD ≤ 9.7%). The validated procedure was successfully used to assess organic solvents levels in a Brazilian radiopharmaceuticals samples manufactured by Radiopharmaceutical Research and Production Unit of Nuclear Technology Development Center (CDTN), in Belo Horizonte (Brazil). The analytes could be well resolved in 1.5 min and accurately determined in three different types of radiopharmaceuticals. This procedure is applicable to samples even with high ethanol content up to 11% (v/v). Other advantages include no sample preparation, short chromatographic separation time and minimum manual operation. As results, the proposed procedure can be useful in the routine analysis for the determination of acetonitrile and ethanol in radiopharmaceutical samples.