Liquid chromatographic method to follow-up ceftazidime and pyridine in portable elastomeric infusion pumps over 24 h

Portable infusion pumps are an interesting solution to continue outpatient parenteral antimicrobial therapy (OPAT) at the patient's home. However, the use of ceftazidime for such applications is challenging in view of its relatively poor stability in solution. In this study, elastomeric infusion pumps with 6 or 7 g of ceftazidime were deflated over 24 h in an oven at 33°C while ceftazidime and its degradation product, pyridine, were regularly monitored. Hereto, a fast and sensitive liquid chromatographic (LC) method has been developed using a Kinetex^® C18 (150 × 3 mm, 2.6 μm) column with gradient elution. Ammonium formate 20 mM and acetonitrile (ACN) were mixed in a ratio of 98:2 v/v for mobile phase A and 85:15 v/v for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was set at 0.4 mL/min. The solution with a starting dose of 6 g ceftazidime was found to be degraded 10% after an average of 19 h 11 min so that an administration of 6 g to the patient was not reached. For the solution with a starting dose of 7 g of ceftazidime, 10% degradation was observed after an average of 18 h 42 min. However, by starting from a higher dose, an average of 6.56 g of ceftazidime could be administered over 24 h. In addition, 1.0% of pyridine versus ceftazidime pentahydrate with sodium carbonate (=mixture for injection) was formed over 24 h.