Stability and Compatibility of Combinations of Hydromorphone and Dimenhydrinate, Lorazepam or Prochlorperazine

Abstract

ABSTRACT The stability and compatibility of combinations of hydromorphone (2, 10 and 40 mg/ml) admixed separately with dimenhydrinate (50 mg/ml), prochlorperazine (5 mg/ml), or lorazepam ( 4 mg/ml) were tested over a seven-day period at 4°C, 23°C and 37°C. In addition to visual inspection and pH, the concentration of each component in the binary mixture was determined by a stability-indicating liquid chromatographic method. Each test was completed at time zero, one, four, six and seven days after mixing equal volumes of each medication. The hydromorphone-dimenhydrinate combination was compatible and stable for 24 hours. By 48 hours, 8-chlorotheophylline had precipitated and the degree of precipitate was enhanced by increasing hydromorphone concentration. Lorazepam was physically compatible with hydromorphone. However, lorazepam degraded such that 90% of the initial concentration was maintained for six days at 4°C, four days at 23°C and only 24 hours at 37°C. Prochlorperazine and hydromorphone were physically compatible for seven days, even though prochlorperazine stability was affected by the presence of hydromorphone. However, less than 10% of the prochlorperazine degraded over seven days, even at 3 7° C We recommend a seven-day expiration date for the combination of hydromorphone and prochlorperazine based on the observed physical and chemical stability of the combination at temperatures up to 37°C. However, we cannot recommend admixing hydromorphone and dimenhydrinate due to the precipitation of 8-chlorotheophylline. Admixtures of hydromorphone and lorazepam were physically compatible but the mixture was limited by the stability of lorazepam and so it is recommended that the expiry date not exceed 96 hours (four days) at 4°C. This will allow the solution to be stored at room temperature for up to an additional 24 hours prior to administration. RESUME On a melange diverses solutions d'hydromorphone (2,10 et 4O mg/mL) avec, separement, un volume egal d'une solution soit de dimenhydrate (50 mg/mL), de prochlorperazine (5 mg/mL) ou de lorazepam (4 mg/mL), pour verifier la compatibilite de ces trois medicaments avec l'hydromorphone et determiner la stabilite du melange binaire pendant sept jours a 4°C, a 23° C et a 37°C. En plus d'effectuer un examen visuel et de determiner le pH, on a dose les composants des melanges par une methode de chromatographie en phase liquide indiquant la stabilite. On a analyse les melanges au moment de leur preparation, puis apres un, quatre, six et sept jours. L 'hydromorphone et le dimenhydrate sont compatibles et leur melange reste stable 24 heures. Cependant, apres 48 heures, la 8-chlorotheoplzylline precipite; la precipitation s'accroit avec la concentration d'hydromorphone. Le lorazepam et l'hydromorphone sont physiquement compatibles. Neanmoins, le lorazepam se degrade, de sorte que le melange ne contient plus que 90% de la concentration initiale de ce medicament apres six jours a 4°C, quatre jours a 23°C et seulement 24 heures, a 37°C. La prochlorperazine et l'hydromorphone sont physiquement compatibles pendant sept jours, mais l'hydromorphone altere la stabilite de la prochlorperazine. La decomposition de cette derniere est toutefois inferieure a 10% apres sept jours meme a 37°C. On recommande de fixer a sept jours la duree de stockage du melange d'hydromorphone et de prochlorperazine, etant donne sa stabilite physique et chimique jusqu'a 37°C. Par contre, melanger des solutions d'hydromorphone et de dimenhydrinate n'est pas indique, en raison de la precipitation de la 8-chlorotheophylline. Les solutions d'hydromorphone et de lorazepam sont physiquement compatibles, mais la stabilite du lorazepam dans le melange etant limitee, on deconseille de le stocker plus de 96 heures (quatre jours) a 4°C. Ceci permettra de stocker la solution a temperature ambiante jusqu'a 24 heures additionnelles avant l'administration.