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.
Highlights
Polymyxins are a group of antibacterial substances developed for clinical use in 1947
The detection was not influenced by the co-elution since it was performed monitoring m/z transitions: m/z 593.7 → m/z 482.20 and m/z 586.7 → m/z 101.00 for polymyxin B1 and B2, respectively (Figure 1)
In this work we proposed and validated an analytical method that can be applied to stability studies of polymyxin B
Summary
Polymyxins are a group of antibacterial substances developed for clinical use in 1947. Polymyxins has reemerged in clinical practice in the last 15 years owing to the worldwide dissemination of extensively-drugresistant Gram-negative infections, notably, Psedomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonia (Pogue, Ortwine, Kaye, 2017). Previous studies reported stability of polymyxins B1, E1 and E2 subjected to different pH values and temperatures (Orwa et al, 2002). The stability of polymyxin B was evaluated in 0.9% saline solutions stored at room temperature and under refrigeration using a microbiological assay (He et al, 2010). In a more recent study the stability of polymyxin B was evaluated in various reduced infusion volumes of 0.045%, 0.225% and 0.9% saline, and 5% dextrose stored at 4, 25 and 30 °C (Lim et al, 2016)
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