达托霉素在不同酸碱条件下产生的杂质及其结构研究

达托霉素是一种正在临床使用的新型抗耐药菌抗生素。由于结构特点,其在不同的pH值下会产生不同的杂质。本文研究了不同pH值下达托霉素杂质的产生情况。利用分析和制备型HPLC,获得了5个主要的相关杂质。通过质谱对各杂质碎片的检测和分析,进行了结构认定。除了4个已知杂质之外,获得了一个未报道的杂质,为达托霉素氨基酸内酰胺断裂后的开环产物。

达托霉素新杂质及其来源研究

达托霉素是一种正在临床使用的新型抗耐药菌抗生素。由于结构特点,其具有很多结构类似的杂质。在达托霉素样品中,通过HPLC分析发现了一种新的杂质,相对保留时间为0.82。经过分离纯化,获得了纯化的新杂质。UPLC-MS检测发现新杂质的分子量为1617。核磁共振分析,确定新杂质的侧链含有双键,推定新杂质为N-(3-癸烯酰基)-L-色氨酰基-D-天冬酰胺酰基-L-天冬氨酰基-1-苏氨酰基-甘氨酰基-l-鸟氨酰基-L-天冬氨酰基-D-丙氨酰基-L-天冬氨酰基-甘氨酰基-D-丝氨酰基-苏-3甲基-l-谷氨酰基-L-3-邻氨基苯甲酰基-L-丙胺酸-ε1-内脂。根据杂质的化学结构,推测该杂质可能来源于发酵过程中补加的类酸。因此通过GC-MS分析了起始原料癸酸,发现其中含有少量癸烯酸,该结果证实了本研究的推测。

Anti-hyperlipidaemic assay and LC-MS/MS determination of piperinic ester in rat

In the present study, we aimed to establish high-fat diet model for evaluating anti-hyperlipidaemic activity of GBA and to establish the HPLC-MS method for measuring the pharmacokinetics of GBA in rat blood plasma and liver after oral administration. Rats were orally administrated with GBA at the dose of 50mg/kg body weight. GBA concentrations in blood plasma and liver were detected by HPLC from 0.5–10 h post administrations. The pharmacokinetic parameters were analyzed by the DAS1.0Software. The concentration-time curves of the plasma GBA and liver GBA wereconformed to two-compartment model. GBA was rapidly absorbed in the gastrointestinal tract and could be detected in plasma and liver 0.5 h after oral administration.