TY - JOUR

T1 - Analytical Control of Impurities and Active Ingredients in a (–)-Isopulegol Derivative with Highly Potent Analgesic Activity

AU - Lastovka, A. V.

AU - Fedeeva, V. P.

AU - Il’ina, I. V.

AU - Salakhutdinov, N. F.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - (2R,4R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol

KW - drug substance

KW - HPLC-UV

KW - validation

KW - DESIGN

KW - 4aR

KW - (2R

KW - VALIDATION

KW - STRUCTURAL-CHARACTERIZATION

KW - 8aR)-4

KW - IDENTIFICATION

KW - HYDROCHLORIDE

KW - 7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-ol

KW - 7R

KW - 4R

UR - http://www.scopus.com/inward/record.url?scp=85085180402&partnerID=8YFLogxK

U2 - 10.1007/s11094-020-02176-0

DO - 10.1007/s11094-020-02176-0

M3 - Article

AN - SCOPUS:85085180402

VL - 54

SP - 190

EP - 194

JO - Pharmaceutical Chemistry Journal

JF - Pharmaceutical Chemistry Journal

SN - 0091-150X

IS - 2

ER -