Purity assessment for 17β-estradiol

Abstract

Purity assessment for high-purity organic substances is regarded as one of the core competences of national metrology institutes. For this reason, Consultative Committee for Amount of Substance—Metrology in Chemistry (CCQM) regularly organized intercomparison studies to compare and demonstrate the degree of equivalence of national measurement capabilities for purity determination. This paper reports the method development work for the participation in a recent CCQM key comparison on purity assessment for estradiol. An indirect consecutive estimation approach was adopted to determine the purity of the estradiol sample, i.e., through the identification and quantification of all possible impurities present in the sample. In the course of assessment, a variety of analytical techniques were applied. The most challenging part was to identify and estimate the amount of unknown organic-related substance present in the testing material. For the moisture determination, a gas chromatography with thermal conductivity detection (GC–TCD) method was employed to supplement the results obtained using coulometric Karl Fischer titration technique. Inorganic impurities and volatile organic compounds residual were analyzed using inductively coupled plasma mass spectrometry (ICP–MS) and gas chromatography–mass spectrometry (GC–MS) techniques, respectively, and their contributions were found to be comparatively insignificant.