Stability of Ampicillin in Normal Saline Following Refrigerated Storage and 24-Hour Pump Recirculation

Abstract

Objective Use of ampicillin in outpatient parenteral antimicrobial therapy (OPAT) has historically been complicated by frequent dosing and limited stability. The purpose of this study was to evaluate stability of ampicillin using high-pressure liquid chromatography (HPLC) in an OPAT dosing model using continuous infusion at room temperature over 24 hours immediately following preparation compared with batches stored under refrigeration for 24 hours, 72 hours, and 7 days. Methods An HPLC method was developed and validated as stability indicating using guidance in USP general Chapter <1225>. Four ampicillin batches were prepared for each experimental condition (immediate use and refrigerated storage for 24 hours, 72 hours, and 7 days). A pump was used to recirculate the solutions through medical-grade tubing for 24 hours. Triplicate 1-mL aliquots were removed from each batch at time 0, 4, 8, 12, and 24 hours and analyzed for ampicillin concentration. Results Each batch was assayed for initial concentration (20.34-21.50 mg/mL), and percent recovery compared with that concentration thereafter. For the duration of infusion, the average recoveries were 96.4%, 95.8%, 94.6%, and 90.3% for immediate use, 24-hour storage, 72-hour storage, and 7-day storage, respectively. The recovery remained above 90% for all batches and time points, except for 7-day storage, which fell below 90% after 4 hours of circulation. Conclusion Ampicillin can be prepared and stored in a refrigerator for up to 72 hours prior to continuously infusing at room temperature over 24 hours with less than a 10% loss of potency over the dosing period. This model supports twice weekly OPAT delivery of ampicillin.