GC Determination of Residual Organic Solvents in Metolazone

Four residual organic solvents,i.e.iso-propanol,ethanol,1,4-dioxane and n-butanol in the drug metolazone were determined by gas chromatography,with PEG-20M capillary column (30 m×0.53 mm) and FID detector under programmed column temperature control,raising from 40 ℃ through 90 ℃ to 180 ℃ within 27.75 min.Temperature at the detector was 250 ℃ and at the sample injector was 145 ℃.Nitrogen was used as the carrier gas with flow-rate of 1.5 mL·min-1.Flow-rates used for hydrogen,air and make-up gas were 35,350 and 46 mL·min-1 respectively.The external standard method was used in the determination.Under the specified analytical conditions,the 4 solvents mentioned above were separated quantitatively.Linear relationships between the peak areas and concentrations of the 4 solvents were obtained as shown by their linear regression equations with correlation coefficients in the range of 0.999 3-0.999 8.Values of detection limits (S/N=3) and determination limits (S/N=10) of the method found were 0.25,5.89,1.66,2.47 mg·L-1 and 17.57,10.99,8.51,6.11 mg·L-1 for iso-propanol,ethanol,1,4-dioxane and n-butanol respectively.Results of recovery test obtained were in the range of 97.9%-101.5%.