注射用头孢噻呋钠在牛奶中的残留消除研究

On the elimination of residues of ceftiofur sodium for injection in milk

旨在分析注射用头孢噻呋钠在牛奶中的残留消除规律,为该药临床合理使用以及制定弃奶期提供依据。选取20头健康奶牛(高产、低产各10头),按每千克体重2.2 mg肌肉注射给药,连续给药3 d,在第1次给药后4、12 h,第2次给药后4、12 h,以及最后1次给药后4、8、10、12、24 h,采集4个乳区的混合奶样,样品用二硫赤藓糖醇提取,再用碘乙酰胺衍生化后经C18固相萃取小柱净化,浓缩复溶后用建立的高效液相色谱-串联质谱法(HPLC-MS/MS)检测牛奶中头孢噻呋钠残留。结果:第3次给药后10 h牛奶中的残留浓度最高,且所有采样点药物浓度都低于最高残留限量(MRL)。参照欧洲药品局对头孢噻呋制定的MRL,计算弃奶期为7.148 h。本试验结果提示头孢噻呋钠消除较快,考虑到临床实际应用,建议弃奶期定为12 h。

The aim of the study was to analyze the residue pattern of ceftiofur sodium for injection in cows, so as to provide a basis for the rational clinical use of the drug and the formulation the cows in the milk abandonment period. 20 healthy dairy cows(10 high yield ones and 10 low yield ones) were selected. The cows were injected with ceftiofur sodium intramuscularly at 2.2 mg/kg according to their body weight for 3 days. Mixed milk samples were collected from four milk zones at 4 and 12 h after the 1 st dose, 4 and 12 h after the 2 nd dose and 4, 8, 10, 12 and 24 h after the last dose. The sample was extracted with dithioerythritol, then derivatized with iodoacetamide and cleaned up by a C18 solid phase extraction column, concentrated and re-solubilized for the determination of ceftiofur sodium residues in milk by established high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). The results showed that the highest residue concentrations were found in the milk samples collected at 10 h after the last administration of the drug whose concentrations were below the maximum residue limits(MRL) at all sampling points. According to the MRL, established by European Medicines Agency(EMA), for ceftiofur, the withdrawal period of milk was calculated to be 7.148 h. The results suggested that ceftiofur sodium for injection was eliminated quickly, and the suggested milk abandonment period was 12 hours.