Rapid quantification of isoflurane in anesthetic nanoemulsions using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR)

Abstract

There is increased research into pharmaceutical nanoemulsions where the timing of quantification of active components can dictate continuous manufacturing production cost and consistency. The goal of this study was development of a rapid quantification method for isoflurane nanoemulsions using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR). Isoflurane was quantified by ATR-FTIR and High-Performance Liquid Chromatography (HPLC). Correlation and agreement between methods was determined to validate the ATR-FTIR procedure. Evaporation rate studies from the nanoemulsions and pure isoflurane were performed. ATR-FTIR values were in agreement and correlated with (HPLC) measurements (calculated Pearson R of 0.99; 99 % confidence interval; P < 0.001). ∼97 % of the values fell within the upper and lower limits of agreement in Bland Altman plot analysis. ATR-FTIR values were obtained within 1 min compared to 25 min for comparable triplicate measurements using HPLC. Evaporative loss from open nanoemulsions was 80x less than that from containers of pure isoflurane. The reformulation of isoflurane into nanoemulsions lowers risk of exposure for clinical staff, demonstrated by the evaporative loss studies. This method could prevent expensive errors in large-scale continuous manufacture and could be used in the production of other nanoemulsified drug formulations.