ОПРЕДЕЛЕНИЕ ОСТАТОЧНЫХ ОРГАНИЧЕСКИХ РАСТВОРИТЕЛЕЙ МЕТОДОМ ГАЗОВОЙ ХРОМАТОГРАФИИ В СУБСТАНЦИИ (2R,4R,4аR,7R,8aR)-4,7-ДИМЕТИЛ-2-(ТИОФЕН-2-ИЛ)ОКТАГИДРО-2H-ХРОМЕН-4-ОЛ, ОБЛАДАЮЩЕЙ АНАЛЬГЕТИЧЕСКОЙ АКТИВНОСТЬЮ

Introduction of a substance into medical practice requires the  indispensable evidence of the  substance purity as early as the stage of preclinical testing. The content of residual organic solvents, which can affect the  pharmacological activity of the  drug, is one of the  indicators of the  substance quality control. Four solvents are used during synthesis and isolation of the substance: dichloromethane, ethyl  acetate, methyl tert -butyl ether (MTBE), and n -hexane. Two methods of determining residual organic solvents in (2 R ,4 R ,4 aR ,7 R ,8 aR )-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2 H -chromen-4-ol using gas  chromatography are offered: i) introduction of a gas sample and separation of the components on a commercial HP-5ms capillary column (30 m × 0.35 mm × 0.25 im); ii) introduction of a liquid  sample and separation  on a capillary column (30 m × 0.32 mm × 0.30 im) filled with  a modified poly(1-trimethylsilyl-1- propyne) (PTMS). Since  the  first method provides only determination of n -hexane and  ethyl  acetate, the  procedure was developed and  validated for determination of four  residual solvents, i.e., dichloromethane, ethyl  acetate, methyl n -butyl ether, and n -hexane in test substance using gas chromatography on the  column with  a modified PTMSP-based phase. We detected trace amounts of ethyl  acetate and  methyl n -butyl ether; the  content of dichloromethane and n -hexane in the  substance appeared below the  detection limits. The average content of ethyl  acetate and MTBE in the  substance for 9 parallel determinations (0.10 and 0.20 ppm) appeared 5 and 2.5 × 104 times lower than maximum permissible content (5000 ppm),  respectively. The  developed technique was assessed for: specificity, linearity of the calibration curve,  correctness, precision at the level of the repeatability and intralaboratory precision, and stability of the  chromatographic system. Standard deviations in the  determination of ethyl acetate and MTBE in the substance do not exceed 0.03 and 0.09, respectively. The procedure is specific, accurate and  reliable for determination of the  residual organic solvents in the  substance.