Ultra Trace-level Determination of Genotoxic Impurity Dimethyl Sulfate in Ciprofloxacin and Its Hydrochloride by Derivation-headspace Gas Chromatography Method

OBJECTIVE To establish a derivation-headspace gas chromatography method for the determination of ultra trace genotoxic impurity dimethyl sulfate in ciprofloxacin and its hydrochloride.

METHODS Using sodium iodide as derivatization reagent, dimethyl sulfate was alkylated to produce iodomethane. The content of dimethyl sulfate was calculated by measuring iodomethane. Column was DB-Wax(30 m×0.53 mm, 1.0 μm), carrier gas was nitrogen. The flow rate was 3.0 mL·min⁻¹. The detector was electron capture detector(ECD). The initial temperature was 60 ℃, hold 2 min, then the temperature was raised to 180 ℃ at 40 ℃·min⁻¹, hold 2 min.

RESULTS There was no interference in the blank test. The linear relationship of dimethyl sulfate in the range of 8.50−63.76 ng·mL⁻¹ was good(r=0.9969), the LOQ was 2.1×10⁻⁹ g·mL⁻¹. The average recovery were 89.3% and 86.6%(n=9) in ciprofloxacin and ciprofloxacin hydrochloride. The residues of dimethyl sulfate in 6 batches of samples were all lower than the LOQ.

CONCLUSION The established method is simple, accurate, sensitive and durable for limit test and quantitative analysis of dimethyl sulfate in ciprofloxacin and its hydrochloride.