An HPLC-UV procedure is proposed for identifying processing impurities and determining the contents of active ingredient in the drug substance of the promising non-narcotic analgesic (2R,4R,4aR,7R,8aR)- 4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol (1). Processing impurities including the starting reagents thiophene-2-carbaldehyde and (–)-isopulegol, a related stereoisomer of 1, and intermediates and dehydration products of 1 could be present as a result of the synthesis and isolation. The developed chromatography conditions could separate possible impurities and analyte 1 with the required resolution. The contents of the studied processing impurities were below the established detection limits of 0.056 μg/mL for thiophene-2-carbaldehyde; 0.32, (–)-isopulegol; 0.22, the stereoisomer; and 0.18, 0.22, and 0.37, for the dehydration products. The working range of concentrations for the procedure was 0.50 – 10 μg/mL. The recovery varied from 98.9 to 101.2% in the accuracy evaluation. The procedure was demonstrated to have sufficient accuracy. The average relative standard deviation in the intraday precision evaluation was 0.7%; in the interday precision assessment, 0.8%, which were below the acceptance criteria of 2.0 and 3.0%, respectively.
- drug substance