Rapid Monitoring and Determination of Class 1 Residual Solvents in Pharmaceuticals Using Dispersive Liquid-Liquid Microextraction and Gas Chromatography-Mass Spectrometry.

A simple and rapid dispersive liquid-liquid microextraction (DLLME) method coupled with gas chromatography-mass spectrometry (GC-MS) for monitoring and determination of class 1 residual solvents, benzene (Bz), carbon tetrachloride (CT), 1,2-dichloroethane (1,2-DCE), 1,1-dichloroethene (1,1-DCE), 1,1,1-trichloroethane (1,1,1-TCE), in pharmaceuticals was developed and evaluated. The parameters affecting the extraction efficiency of analytes such as type and volume of extraction solvent, type and volume of dispersive solvent and ionic strength were investigated and optimized. 1-Octanol and methanol proved to be the most suitable extraction and dispersive solvents, respectively. The method showed linearity for 1,1-DCE, 1,1,1-TCE, CT, Bz and 1,2-DCE in the ranges of 0.001-80, 0.005-80, 0.002-80, 0.0001-40 and 0.001-80 µg/mL, respectively. The relative recoveries were in the range of 84-92, 87-98, 83-94, 89-98 and 87-96% for 1,1-DCE, 1,1,1-TCE, CT, Bz and 1,2-DCE, respectively. The obtained results showed that the proposed method can be used to monitor and determine class 1 residual solvents in pharmaceuticals.