ABSTRACT
OBJECTIVE: The post-reconstitution chemical stability and microbial challenge hold time of nonpreserved telavancin for injection was determined using common reconstitution diluents and intravenous (IV) infusion solutions stored at room temperature with light (ambient) or at 2°C to 8°C without light (refrigeration). METHODS: Telavancin was reconstituted with 5% dextrose, 0.9% normal saline, or sterile water (15 mg/mL). Infusion solutions at 0.6 and 8.0 mg/mL were prepared in ViaFlex (polyvinyl chloride) IV bags (Baxter International Inc, Deerfield, Illinois) using 5% dextrose, 0.9% normal saline, or lactated Ringer's solution. Chemical stability was evaluated for up to 14 days under refrigeration and for up to 3 days under ambient conditions. Telavancin concentration and degradant levels were determined using a stability-indicating HPLC method. Solutions were subjected to microbial-challenge testing for up to 48 hours (ambient) or for up to 6 days (refrigeration). RESULTS: All reconstituted or infused telavancin solutions met the prespecified stability acceptance criteria after 2 days under ambient and minimum 7 days under refrigeration. Following inoculation with gram-positive and gram-negative microorganisms, telavancin infusion solutions stored under ambient conditions reduced or inhibited populations of all organisms up to 48 hours, except for Serratia marcescens, which exhibited growth of >0.5 log10 after 12 hours. All refrigerated samples inhibited or reduced bacterial populations up to 6 days. CONCLUSIONS: These results are supportive of a total hold time for reconstituted telavancin in vials plus the time in IV infusion solutions in polyvinyl chloride bags to not exceed 12 hours under ambient conditions and 7 days under refrigeration.
ABSTRACT
A reversed phase HPLC method developed for a drug product formulation using hydroxypropyl-beta-cyclodextrin (HPCD) was rendered ineffective for analyzing a similar formulation containing sulfobutylether-beta-cyclodextrin (SBECD). The active pharmaceutical ingredient (API) and the majority of its impurities became more strongly retained, eluting as an incoherent conglomerate of peaks. Furthermore, this phenomenon was reproduced in subsequent injections of the API reference standard. Based on HPLC and LC-ESI-MS studies, the chromatography failure was attributed to the accumulation of SBECD on the HPLC column. The subsequent interaction of the API with bound SBECD resulted in the aberrant chromatography. An anion-exchange solid-phase extraction treatment was developed and qualified to selectively remove SBECD from sample solutions, thereby allowing the same HPLC method to be used. The sample treatment procedure exhibited suitable accuracy and precision for quantitating the API and its impurities, and resulted in typical chromatographic profiles.
