Compatibility and stability of dezocine and tropisetron in 0.9% sodium chloride injection for patient-controlled analgesia administration

Abstract

Tropisetron is an adjuvant for dezocine used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the institutional incidence of postoperative nausea and vomiting (PONV), which decreases resource utilization and cost. However, no scientific evidence has been reported in the literature demonstrating analytical confirmation of the compatibility and stability of the combination of dezocine and tropisetron. Thus, the present study aimed to investigate the stability of dezocine with tropisetron in 0.9% sodium chloride injection form for PCA administration.Commercial solutions of dezocine and tropisetron were combined and examined for compatibility and stability when diluted with 0.9% sodium chloride injection in polyolefin bags and glass bottles stored at 4°C or 25°C for up to 14 days. The initial concentrations were 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron. For all samples, the compatibility parameters (including precipitation, cloudiness, discoloration, and pH values) were evaluated. Chemical stability was also determined using high-performance liquid chromatographic (HPLC) analysis.After a 14-day period of storage at 4°C or 25°C, the initial concentrations of dezocine and tropisetron were maintained at at least 98%. All of the mixtures remained clear and colorless throughout the observation period, and no color change or precipitation was observed.These results indicated that admixtures of 40 mg/100 mL dezocine and 5 mg/100 mL tropisetron in 0.9% sodium chloride injection were stable for at least 14 days when stored in polyolefin bags or glass bottles at 4°C or 25°C and protected from light.

Figure 1

Structures of (A) dezocine and (B) tropisetron hydrochloride.

Figure 2

Chromatograms of dezocine 0.4 mg/mL and tropisetron hydrochloride 0.05 mg/mL admixtures that were freshly prepared (A) exposed to 0.1 mol/L hydrochloric acid at 60°C for 5 hours (B) exposed to 0.1 mol/L sodium hydroxide at 60°C for 5 hours (C) and exposed to 3% hydrogen peroxide at 60°C for 5 hours, (D) dezocine elutes at 6.48 minutes (peak 1) and tropisetron hydrochloride at 11.04 minutes (peak 2).

Figure 3

Typical chromatograms of dezocine and tropisetron hydrochloride mixtures on study day 14. Mixtures stored at 25°C in glass containers (A) and polyolefin bags (B) mixtures stored at 4°C in glass containers, (C) and polyolefin bags, (D) dezocine elutes at 6.48 minutes (peak 1) and tropisetron hydrochloride at 11.04 minutes (peak 2). Degradation products found during the accelerated degradation study are not readily apparent in these chromatograms and did not increase in quantity during the study period.