Physicochemical stability of ternary admixtures of butorphanol, ketamine, and droperidol in polyolefin bags for patient-controlled analgesia use.

BACKGROUND: Delivery of drug admixtures by intravenous patient-controlled analgesia is a common practice for the management of postoperative pain; however, analytical confirmation of the compatibility and stability of butorphanol tartrate, ketamine hydrochloride, and droperidol combined in ternary admixtures is not available. METHODS: Butorphanol tartrate, ketamine hydrochloride, and droperidol have been examined for compatibility and stability when combined with 0.9% sodium chloride injection stored at 4°C and 25°C with light protection for a total of 14 days. Concentrations were 0.067 mg/mL, 1.33 mg/mL, and 0.033 mg/mL for butorphanol tartrate, ketamine hydrochloride, and droperidol, respectively. Drug concentrations were determined using high-performance liquid chromatographic analysis. RESULTS: All three drugs were very stable (>97%) at 4°C and 25°C for 14 days. The ternary admixtures were initially clear and colorless throughout the observation period, and the pH value did not change significantly. CONCLUSION: The results confirm that the ternary admixture of butorphanol tartrate 0.067 mg/mL, ketamine hydrochloride 1.33 mg/mL, and droperidol 0.033 mg/mL in 0.9% sodium chloride injection were stable for 14 days when stored in polyolefin bags at 4°C and 25°C and protected from light.

Separation of enantiomers of butorphanol and cycloamine by capillary zone electrophoresis.

Butorphanol tartrate is a synthetic opioid agonist-antagonist used as analgesic, possessing three chiral centres in the basic part of the molecule. Its chiral purity is routinely controlled only by optical rotation. A new capillary zone electrophoresis method, capable to separate the enantiomers of butorphanol and intermediate of its synthesis, cycloamine, was developed. Different electrolyte composition (type and concentration of carrier ion, pH, and organic solvent addition), and type and concentration of several chiral selectors (natural and modified cyclodextrins) were tested. Using the optimized conditions (acidic electrolyte with the addition of highly sulphated gamma-cyclodextrin) as low as 0.05% of undesirable enantiomers can be detected. Selected method characteristics, i.e., linearity (0-50 mg/l), precision (2.5% at 20 mg/l), and accuracy (101 +/- 2% at 20 mg/l) were evaluated. The optimized method was applied for the analysis of real batches of butorphanol and cycloamine. It was found that butorphanol tartrate manufactured by IVAX Pharmaceuticals contains less than 0.05% of undesirable enantiomer.