Evaluation of the stability of Polymyxin B in saline and glucose solutions using LC-MS/MS

Abstract

Polymyxins are a group of antibacterial substances and have remained the drugs of choice for treatment of resistant Gram-negative bacilli. Polymyxin B is administered by intravenous infusion and requires the reconstitution of lyophilized powder with 0.9% saline or 5% glucose solutions. To date, there is little information about polymyxin stability in different infusions solutions, especially at 40 ºC, a temperature that is recommended to study drug stability as it accelerates degradation reactions. Therefore, in this work an analytical method using LC-MS/MS was developed, validated and applied to determine the stability of polymyxin B diluted in 0.9% saline or 5% glucose solutions at 25 ºC and 40 ºC. The stability of polymyxin B solutions was evaluated during 72 hours. Polymyxin B1 and B2 were stable for 24 hours in saline (0.9%) and glucose solution (5%), however a significant degradation of polymyxin B1 and B2 was observed after 48 hours and 72 hours of assay. The reduction of polymyxin content was evidenced in both saline and glucose media, at room temperature as well as at 40 °C. No significant differences in pH of polymyxin solutions (glucose or saline) were evidenced during stability assay.