Trace Determination of Dimethyl sulfate in Clopidogrel bisulfate by GC-MS

OBJECTIVE To establish a head space gas chromatography mass spectrometry(HS-GC-MS) analytical method for the trace determination of dimethyl sulfate in clopidogrel bisulfate. METHODS The analytical column was DB-624(30 m×0.32 mm, 1.5 μm). The column temperature was maintained at 40℃, holding for 8 min, then was raised to 220℃ at the rate of 30℃·min^-1, holding for 2 min. The flow rate of carrier gas helium was 2.0 mL·min^-1. The detection was achieved in electron impact ionization(EI), and the selected ions were m/z 45, 56 and 88 in the selected ion monitoring mode. RESULTS The calibration curve of dimethyl sulfate was in a good linearity over the range of 0.15-3.0 μg·mL^-1(r²=0.994 2). The limit of detection was 0.05 μg·mL^-1, and the limit of quantification was 0.15 μg·mL^-1. The average recovery of dimethyl sulfate was 83.9%, and the RSD(n=9) was 4.0%. There was a little of dimethyl sulfate detected in one batch of clopidogrel bisulfate sample. CONCLUSION The method is easy to operate, accurate in results and high in sensitivity, which is applicable for the quality control of dimethyl sulfate in clopidogrel bisulfate.