目的 采用HPLC-MS法鉴定制霉素和制霉菌素中组分，并对其潜在毒性进行预测。方法 采用HPLC-MS法测定，Sepax Bio-C₁₈色谱柱（250 mm×4.6 mm，5 μm）；流动相：[0.38%乙酸铵溶液–乙腈（71∶29）]–[0.38%乙酸铵溶液–乙腈（40∶60）]，梯度洗脱；检测波长305 nm；体积流量1.0 mL/min；柱温30℃；进样量20 μL。采用电喷雾正离子化（ESI），扫描范围m/z 100～1 700，碎裂电压100 V，毛细管电压3 500 V，雾化气压45 psi，干燥气流速10 psi，干燥气温度325℃；无二级质谱。结果 制霉素中主要成分为制霉菌素A₃、多真菌素B、制霉菌素A₁和白诺菌素，制霉菌素A₃、多真菌素B分子中具有L-洋地黄毒糖结构，白诺菌素分子中具有2，5-二酮哌嗪结构。制霉菌素以制霉菌素A₁为主要成分，制霉菌素A₁分子中无洋地黄毒糖或2，5-二酮哌嗪结构。结论 制霉素、制霉菌素中主要成分和含量均不相同，制霉素组分中的L-洋地黄毒糖结构和2，5-二酮哌嗪结构可能分别导致心脏毒性和生殖毒性。

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.

R286.02