RESUMEN
A simple and sensitive method for simultaneous determination of 12 kinds of residual solvents in a new drug CBT108 was established and validated by headspace gas chromatographic technology. The rationality,accuracy and feasibility of the analytical method were verified. Under the optimized conditions, simultaneous separation and determination of 12 kinds of residual solvents, including methanol, ethanol, ether, acetone, acetonitrile, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, heptane, toluene and carbon tetrachloride was carried out by using a DB624 capillary column(30 m×0.53 mm×3.0 μm) for separation, a flame ionization detector for detection and internal standard method for quantitation. Good linearity was obtained for 12 solvents with the correlation coefficients(R2) of more than 0.997. The limits of quantitation and detection were defined at S/N=3 and S/N=10,respectively. LOQ and LOD for 12 solvents were given as 0.024 μg/mL and 0.0072 μg/mL for methanol,0.1 μg/mL and 0.012 μg/mL for ethanol, 0.01 μg/mL and 0.005 μg/mL for ether, 0.1 μg/mL and 0.008 μg/mL for acetone, 1.025 μg/mL and 0.0615 μg/mL for acetonitrile, 0. 09 μg/mL and 0. 06 μg/mL for dichloromethane, 0. 09 μg/mL and 0.06 μg/mL for n-hexane, 0. 25 μg/mL and 0. 008 μg/mL for ethyl acetate, 0. 108 μg/mL and 0.014 μg/mL for tetrahydrofuran,0.16 μg/mL and 0.0004 μg/mL for carbon tetrachloride,0.0075 μg/mL and 0.005 μg/mL for heptane, and 0.0445 μg/mL and 0.0014 μg/mL for toluene. The adding standards recoveries for 12 residual solvents at three spiked levels were in the range of 90.96%-108.67%,with relative standard deviations of 0.1%-5.7%. This simple,high accuracy and good repeatability method is feasible for rapidly determination of 12 residual solvents in drug candidate CBT108. Meanwhile, this simple method provides a consulted value for detection of residual solvents in other medicines.