Development of an HPLC method for the radiochemical purity evaluation of [18F]fluoroestradiol

Abstract

18F-Fluoroestradiol ([18F]FES), an estrogen analog, is a radiopharmaceutical used in Positron Emission Tomography (PET) that allows evaluating the tumor cell receptor profile and the best therapy strategy, the staging, the prognosis and the response to therapy in several breast cancer cases. As there is not any pharmacopoeia’s monograph of [18F]FES to standardize its quality control criteria, this work presents a new HPLC’s method to perform the [18F]FES radiochemical purity. A liquid chromatograph was used with radioactivity and ultraviolet detectors. Three concentrations of fluoroestradiol standard solution were used along the test. Their retention time was compared to its relative radiolabelled analogue to confirm its identity. Several mobile phases with acetonitrile and two mobile phase flows were tested to optimize the runs. Peaks symmetry, retention time, theoretical plates and resolution were analyzed to choose the best conditions. The mean retention time of both standard Fluoroestradiol and [18F]FES solutions were the same, demonstrating that [18F]FES formulation did not interfere with [18F]FES analysis. The best conditions were 1.2 mL/min and isocratic 40% V/V acetonitrile in water, which gave [18F]FES peak resolution greater than 6 and symmetry factor of 1. Thus, the developed method is ready to be validated and implemented in [18F]FES quality control routine in CDTN/Brazil.

Radiochemical Purity and Identity in Radiopharmaceuticals: Design and Improvement of Quality Control Methods by HPLC

“…In the represented structure, the main chromophore can be observed in red as the aromatic ring in conjugation. Although the absorption region between 260 and 290 nm may be more selective and some authors use it for quantification [14][15][16][17], it is possible to increase the sensitivity of the method by using the band from 225 to 235 nm, taking care not to approach the cut-off zone of the solvents used in the mobile phase.…”

Synthesis and characterization of the radiopharmaceutical [18F]fluoroestradiol

“…The methodologies used in the assays of [ 18 F]FES were based on the work of Kuntzsch et al [16] (chemical purity), the work of Bispo et al [17] (radiochemical identity and purity), the techniques used for [ 18 F]fluorocholine analyses (pH assay) and for [ 18 F]FDG analysis (residual solvents, radionuclidic identity and purity) described in the US Pharmacopeia [18].…”

“…The chemical purity test, which determines the concentration of TBA-HCO 3 used as phase catalyst, was performed as described by Kuntzsch et al [16]. The radiochemical identity and purity tests were based on work of Bispo et al [17] with modifications in order to improve the peaks resolution for [ 18 F]FES.…”

Method development, validation, and impurity measurement of β-estradiol from radiolabeled [131I]β-estradiol using radio-high-performance liquid chromatography for radioligand of saturation binding assay

“…have also developed a method to validate [ 18 F] fluoroestradiol using reversed-phase HPLC (RP-HPLC). [ 17 ]…”