Identification and Quantification by NMR Spectroscopy of the 22 R and 22 S Epimers in Budesonide Pharmaceutical Forms

The authors developed four variants of the qNMR technique (¹H or ¹³C nucleus, DMSO-d6 or CDCl₃ solvent) for identification and quantification by NMR of 22R and 22S epimers in budesonide active pharmaceutical ingredient and budesonide drugs (sprays, capsules, tablets). The choice of the qNMR technique version depends on the drug excipients. The correlation of ¹H and ¹³C spectra signals to molecules of different budesonide epimers was carried out on the basis of a comprehensive analysis of experimental spectral NMR data (¹H-¹H gCOSY, ¹H-¹³C gHSQC, ¹H-¹³C gHMBC, ¹H-¹H ROESY). This technique makes it possible to identify budesonide epimers and determine their weight ratio directly, without constructing a calibration curve and using any standards. The results of measuring the 22S epimer content by qNMR are comparable with the results of measurements using the reference HPLC method.