Determination of Organic Solvent Residues in Active Pharmaceutical Ingredients of Apremilast by Gas Chromatography
Objective To establish a gas chromatography method for determination of eight organic solvent residues in active pharmaceutical ingredients(API)of apremilast.Methods The chromatographic column was DB-624 quartz capillary column(60 m×0.53 mm,3.00 µm)with temperature programming,the inlet temperature was 220℃,the detector was flame ionization detector(FID)with temperature of 250℃,the carrier gas was nitrogen with the flow rate of 4 mL/min,the split ratio was 20∶1,and direct injection was adopted with injection volume of 1 µL.Results The linear ranges of methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol were 9.361-593.2 µg/mL,10.01-984.6 µg/mL,10.23-996.4 µg/mL,14.31-971.5 µg/mL,10.22-991.4 µg/mL,7.313-983.3 µg/mL,3.335-201.6 µg/mL,10.12-202.4 µg/mL(r≥0.999 8,n = 4),respectively.The limits of quantification(LOQ)were 9.36,10.01,10.23,14.31,10.22,7.31,3.34,and 10.12 µg/mL,respectively.The limits of detection(LOD)were 2.81,3.00,3.07,4.29,3.07,2.19,1.01,and 3.37 µg/mL,respectively.The RSDs of precision and repeatability test results were less than 6.0%(n = 6).The average recoveries of methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol were 103.25%,103.97%,101.51%,103.58%,102.63%,100.92%,103.67%,and 103.63%with RSDs of 2.24%,5.70%,2.15%,1.92%,2.25%,4.54%,3.28%,and 0.95%(n = 9),respectively.The contents of ethanol in the three batches of samples were 0.17%,0.16%,and 0.19%,respectively.The contents of acetone in the three batches of samples were 0.20%,0.17%,and 0.21%,respectively.No other solvents were detected.Conclusion The method is simple,accurate and reliable with high sensitivity,which can be used for the determination of eight types of organic solvent residues in the API of apremilast.The residual limits for methanol,ethanol,acetone,methyl acetate,ethyl acetate,acetic acid,isopropyl deneacetone,and diacetone alcohol in the API of apremilast are set as 0.3%,0.5%,0.5%,0.5%,0.5%,0.5%,0.1%,and 0.1%,respectively.
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