Stability of apomorphine hydrochloride in aqueous sodium bisulphite solutions

Stability of apomorphine in solutions containing selected antioxidant agents

“…Interestingly, the results from sections “Stability of 10 mg/mL and 50 μg/mL (with and without acetate buffer) apomorphine HCl in 0.1% SMB solutions (purged with nitrogen)” and “Stability of apomorphine HCl solutions (10 mg/mL; without nitrogen purging) in 0.1% AA solution and 0.1% EDTA solutions” showed that apomorphine HCl in all 10 mg/mL samples remained stable, where the concentration of sample solutions were within 95%–105% with no discoloration during the study period, when subjected to either 0.1% SMB solutions (purged with nitrogen), 0.1% AA solution (without nitrogen purging) or 0.1% EDTA solution (without nitrogen purging). As discussed in the “Introduction” section, the similar concentration-dependent degradation pattern was also observed by Ng Ying Kin et al, 7 where the authors described that 0.1 mg/mL apomorphine HCl in 0.125% SBM solution retained approximately 50% of its initial concentration after 6 weeks (with discoloration of solution after 3 weeks) when incubated at 4°C, while the counterpart 1 mg/mL apomorphine HCl in 0.125% SBM solution retained at least 95% of its initial concentration under the same incubation conditions. Similarly, Priston and Sewell 18 also found that 10 mg/mL apomorphine HCl formulated in 0.1% SMB did not change in color and pH value with 98% remaining at 8°C after 14 days and with 96% remaining at 37°C after 7 days.…”

“…Similarly, Priston and Sewell 18 also found that 10 mg/mL apomorphine HCl formulated in 0.1% SMB did not change in color and pH value with 98% remaining at 8°C after 14 days and with 96% remaining at 37°C after 7 days. The results from Ng Ying Kin et al 7 and Priston Sewell 18 indicated that apomorphine HCl solution with a higher concentration was more stable than its counterpart with a lower concentration. On the other hand, it is postulated that the 10 mg/mL apomorphine HCl in 0.1% AA solution and the 10 mg/mL apomorphine HCl in 0.1% EDTA solution in the “Stability of apomorphine HCl solutions (10 mg/mL; without nitrogen purging) in 0.1% AA solution and 0.1% EDTA solutions” section might have changed color if the study period was prolonged.…”

“…The initial pH of the sample solution could affect the rate of degradation of apomorphine, and a color change in solution was an important indication of instability of the solution. Similarly, Ng Ying Kin et al 7 found that 1 mg/mL apomorphine solution including 0.125% SMB was stable for more than 6 months at 4°C. In addition, they reported that apomorphine solution was less stable at a lower concentration (0.1 mg/mL), despite the addition of SMB and storage at low temperature (ie, 4°C), suggesting that SMB, which is a common antioxidant added to stabilize apomorphine injection formulation available on the market, might not be effective in preventing the degradation of apomorphine in solution.…”

“…Although the mechanism of autoxidation has been studied extensively in recent years, there are only a few studies that have investigated formulation factors aimed to improve the stability of apomorphine in aqueous solution. 7 – 9 For example, Wilcox et al 9 identified that the addition of ascorbic acid or sodium metabisulfite (SMB) to apomorphine solution, at room temperature, could only significantly delay oxidation of apomorphine in solution for less than 1–3 days. The author also established that a higher concentration of antioxidant and lower storage temperature could also significantly reduce the rate of oxidation of apomorphine.…”

Allergic contact dermatitis caused by apomorphine hydrochloride in a carer

“…Apomorphine hydrochloride may be administered subcutaneously, nasally, rectally or sublingually; however, it cannot be given orally, because of its high first‐pass metabolism (6). It is susceptible to air‐induced and light‐induced decomposition, so an antioxidant, such as sodium metabisulfite, is routinely added to commercialized preparations (7).…”