Abstract

Ceftaroline fosamil (prodrug) and ceftaroline (active form; degradation product) were simultaneously determined by a new stability-indicating HPLC method. These two forms were monitored during stability investigation of drug formulation reconstituted solution following the same conditions used for clinical use (refrigeration and room temperature). In general terms, ceftaroline fosamil is stable when stored at refrigerator until 48 h, with a drug residual content of 93.99% (in saline diluent) and 97.18% (in 5% glucose diluent). At room temperature, its chemical stability is critical, being necessary attention in the time infusion. Ceftaroline free basis was formed during stability testing, and its concentration has increased along the time. A forced degradation study was also performed for evaluation of the main degradation products, which were identified by LC-MS analysis. Applying selected stress conditions, five degradation products were structurally identified, with variation on side chain and cephalosporinic ring. The opened β-lactam ring and ceftaroline free basis can be highlighted.

摘要

通过新的稳定性指示 HPLC 方法同时测定头孢洛林酯（前药）和头孢洛林（活性形式；降解产物）。在药物制剂重构溶液的稳定性研究过程中，按照与临床使用相同的条件（冷藏和室温）监测这两种形式。一般来说，头孢洛林酯在冰箱保存48小时内是稳定的，药物残留含量为93.99%（在盐水稀释液中）和97.18%（在5%葡萄糖稀释液中）。在室温下，其化学稳定性至关重要，输液时必须注意。在稳定性测试过程中形成了头孢洛林游离碱，并且其浓度随着时间的推移而增加。还进行了强制降解研究以评估主要降解产物，通过LC-MS分析鉴定。应用选定的应力条件，从结构上鉴定出五种降解产物，其侧链和头孢菌素环存在变化。可以突出显示打开的 β-内酰胺环和头孢洛林游离基。