The objective of this study was to evaluate the physical and chemical stability of hydromorphone hydrochloride and bupivacaine hydrochloride in concentrations of 15 mg.ml-1 and 10 mg.mL-1 in 0.9% sodium chloride injection. Test samples of hydromorphone/bupivacaine mixtures were stored at 37°C, body temperature encounterd during continuous intrathecal infusion, for 90 days. The solutions were packaged in 20 ml plastic syringes. Evaluations for physical and chemical stability were performed initially and throughout the storage periods. Physical stability was assessed by visual observation. The chemical stability of the drug was evaluated by means of a stability-indicating high-performance liquid chromatographic (HPLC) analytical technique. In addition, pH and osmolarity were measured electronically.
This study determines the stability and compatibility of hydromorphone (15 mg.ml-1) and bupivacaine (10 mg.ml-1) mixture after 3 months at 37°C using a validated method by HPLC-UV. A simple, precise, specific and accurate reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated. The different analytical performance parameters such as linearity, accuracy, specificity, precision and sensitivity (limit of detection and limit of quantitation) were determined according to International Conference on Harmonisation ICH Q2 (R1) guidelines. RP-HPLC was conducted on a nucleoshell RP18plus (C18 150x4.6 mm with 2.7 µm particle size) column. The mobile phase consisted of buffer A (phosphate buffer (0.05M) pH 4.5) and acetonitrile B. The gradient used for the elution is the following one: time (min)/% of B: 0 min/20%; 1.9 min/50%; 2.5 min /40%; 4.5 min/40%; 5.5 min/20%; and 8 min /20%, and the flow rate was maintained at 1.0ml.min–1 and performed at 35°C. The molecules were monitored using Dionex ultimate 3000, equipped with photo diode array detector (=210 nm). Linearity was observed in concentration range of 9–21 mg.l-1 for hydromorphone and 6-14 mg.l-1 for bupivacaine. All the system suitability parameters were found within the range.
The degradation study shows a photolytic degradation compound for hydromorphone and an oxidative degradation compound found for bupivacaine. The stability study shows no visible haze or particulate formation or gas evolution. pH and osmolarity were stable during the 3 months. Colour changed after 2 months, although this colouring is due to hydromorphone, proportional to hydromorphone concentrations and increases with time but it is a well known modification. The quantitative study by HPLC method revealed no significant change in hydromorphone and bupivacaine concentration. There is less than 5% of variability during the 3-month period.
Hydromorphone (15 mg.ml-1) and bupivacaine (10 mg.ml-1) were physically and chemically compatible and analysed with HPLC, which revealed no significant change in hydromorphone and bupivacaine concentration in this simulated compatibility study.