Chemical stability and compatibility of acetaminophen injection with six common opioid drugs: implications for clinical use.

Despite the clinical importance of combining acetaminophen and opioids in multimodal analgesia, their compatibility has not been determined. This study aimed to investigate the stability and feasibility of mixing acetaminophen injection with six commonly used opioid drugs. Acetaminophen injection was mixed with each of the six opioid drugs at room temperature (25°C). Changes in appearance, pH, and acetaminophen concentrations were monitored at different time intervals to evaluate compatibility. Compatibility was defined as no visible changes, pH variation <1.0, and acetaminophen concentration ≥90% of baseline. The results indicated that acetaminophen injection, when mixed with six commonly used opioid drugs, remained stable for up to 48 h at room temperature. No significant changes were observed in the appearance of the mixtures, which remained clear and free of precipitation. The pH of the mixtures fluctuated by less than 1.0 unit, and the acetaminophen concentration remained above 90% of the baseline value, with a variation of less than 10%. Acetaminophen injection was compatible with morphine, sufentanil, hydromorphone, pentazocine, butorphanol, and nalbuphine for at least 48 h at 25°C, supporting their co-use in patient-controlled intravenous analgesia. Further studies should define pharmacokinetics and adverse effects of these combinations.