Stability of sufentanil citrate with levobupivacaine HCl in NaCl 0.9% infusion after microwave freeze-thaw treatment.

Background: Sufentanil is a powerful central anesthetic and analgesic of the opiate family that can be used with levobupivacaine for epidural administration. Advance preparation of intravenous solution could be useful to improve quality, time management, and cost-savings of drug delivery.
Objective: To investigate how freezing, long-term storage, and microwave thawing can affect the stability of sufentanil citrate and levobupivacaine HCl in NaCl 0.9% (saline) (w/v) polyvinyl chloride (PVC) bags.
Methods: The stability of 5 bags of solution containing sufentanil 500 microg and levobupivacaine 625 mg per 500 mL of saline solution in PVC bags was studied after freezing for 4 months at -30 degrees C, thawing in a microwave oven with a validated cycle, and storage at 4 degrees C. The concentrations of the drugs were measured by HPLC using a reversed-phase column, a mobile phase consisting of 18% acetonitrile (v/v) in tertabutyl ammonium hydrogen sulfate buffer 0.03 M pH 3.00 +/- 0.05, and UV detection at 235 nm for sufentanil and 260 nm for levobupivacaine. Visual inspection and pH measurement were also performed.
Results: No color change or precipitation was observed. Sufentanil and levobupivacaine were stable for at least 70 days at 4 degrees C after freezing and thawing. Throughout this period, the 95% lower confidence limit of the concentration-time profile remained >90% of the initial concentration. During this period, the pH value remained stable.
Conclusions: Within the limits defined here, a mixture of sufentanil citrate and levobupivacaine HCl may be prepared in advance and kept frozen.