[關鍵詞]
[摘要]
目的 采用HPLC-MS法鑒定制霉素和制霉菌素中組分,并對其潛在毒性進行預測。方法 采用HPLC-MS法測定,Sepax Bio-C18色譜柱(250 mm×4.6 mm,5 μm);流動相:[0.38%乙酸銨溶液–乙腈(71∶29)]–[0.38%乙酸銨溶液–乙腈(40∶60)],梯度洗脫;檢測波長305 nm;體積流量1.0 mL/min;柱溫30℃;進樣量20 μL。采用電噴霧正離子化(ESI),掃描范圍m/z 100~1 700,碎裂電壓100 V,毛細管電壓3 500 V,霧化氣壓45 psi,干燥氣流速10 psi,干燥氣溫度325℃;無二級質譜。結果 制霉素中主要成分為制霉菌素A3、多真菌素B、制霉菌素A1和白諾菌素,制霉菌素A3、多真菌素B分子中具有L-洋地黃毒糖結構,白諾菌素分子中具有2,5-二酮哌嗪結構。制霉菌素以制霉菌素A1為主要成分,制霉菌素A1分子中無洋地黃毒糖或2,5-二酮哌嗪結構。結論 制霉素、制霉菌素中主要成分和含量均不相同,制霉素組分中的L-洋地黃毒糖結構和2,5-二酮哌嗪結構可能分別導致心臟毒性和生殖毒性。
[Key word]
[Abstract]
Objective To identify constituents in nysfungin and nystatin by HPLC-MS and prediction of their potential toxicity. Methods HPLC-MS method was used. The determination was carried out on Sepax Bio-C18 column (250 mm×4.6 mm, 5 μm). The mobile phase consisted of 0.38% ammonium acetate solution-acetonitrile (71:29) and 0.38% ammonium acetate solution-acetonitrile (40:60) with gradient elution. The flow rate was 1.0 mL/min, the column temperature was 30℃, the injection volume was 20 μL, and the detection wavelength was 305 nm. The detector was TOF Mass Spectrometer equipped with an ESI ion source and its scanning range was between m/z 100-1 700. Fragmentation voltage was 100 V. Capillary voltage was 3 500 V with atomizing air pressure of 45 psi. The dry gas flow and dryer temperature were 10 psi and 325℃, respectively. Results The main compositions of nysfungin were nystatin A3, polyfungin B, nystatin A1, and albonoursin. Nystatin A3 and polyfungin B had structure of L-digitoxose. Albonoursin had structure of 2,5-diketopiperazine. Nystatin was mainly composed of nystatin A1 which had no L-digitoxose or 2, 5-diketopiperazine structure. Conclusion The main compositions and contents in nysfungin and nystatin are different. The L-digitoxose structure and the 2,5-diketopiperazine structure in the compositions in nysfungin may lead to cardiotoxicity and reproductive toxicity, respectively.
[中圖分類號]
R286.02
[基金項目]