UHPLC-HRMS定量检测莫西沙星中5种亚硝胺类化合物

目的基于超高效液相色谱和高分辨质谱建立同时检测莫西沙星中5种亚硝胺类基因毒性杂质的定量分析方法。方法采用ACE Excel 1.7 C_(18)-PFP(100 mm×2.1 mm,1.7μm)色谱柱,0.1%甲酸水-甲醇为流动相,0.3 mL·min^(-1)的流速进行梯度洗脱。采用四极杆高分辨静电场轨道阱质谱在电喷雾正离子条件下运用平行反应监测模式对5种亚硝胺类化合物进行定量检测。结果5种亚硝胺类基因毒性杂质的定量限均≤0.5 ng·mL^(-1)。NPYP、NEMA和NDEA的标准曲线在1.0~100 ng·mL^(-1)(NPIP和NDBA为0.1~100 ng·mL^(–1))呈良好线性关系(R^(2)≥0.998)。该方法在盐酸莫西沙星药物中的回收率为93.1%~114.1%,RSD为0.7%~4.6%。结论本方法结果准确、灵敏度高、重复性好,适用于盐酸莫西沙星中亚硝胺类基因毒性杂质的含量检测。

Syntheses of Lactam Derivatives of Chenodeoxycholic Acid and in vitro Antiproliferative Activity

With chenodeoxycholic acid as starting material,a series of lactam derivatives of chenodeoxycholic acid was synthesized and their antiproliferative activities against some cancer cells were determined.Among the synthesized derivatives,compounds 6 and 18 displayed distinct antiproliferative activity against PC-3,H-292,SKBR3 and Hey-1B cancer cells,and compounds 10,17 and 18 showed significant antiproliferative activity against SKBR3 cells.Our results reveal that the position of hydroximino on ring A or B of the parental scaffold dramatically affects the antiproliferative activity of these compounds.The conversion of 7-hydroximino to other substituent or 7-hydroximino to 3-hydroximino in the compounds resulted in a dramatic decrease of the antiproliferative activity,suggesting the importance of 7-hydroximino group for the biological activity of the compounds.The structure/activity correlation generated from the studies provides valuable information for the further design of novel chemotherapeutic drugs.