Submicellar liquid chromatography with fluorescence detection improves the analysis of naproxen in plasma and brain...

Rapid, simple, and sensitive submicellar liquid chromatography with fluorescence detection was developed and validated to quantify naproxen in plasma and brain samples after oral administration of Naproxen formulations. The method used tramadol as an internal standard. Different submicellar mobile phases with organic phases ranging from 40 to 60% were studied to improve the native fluorescence of the Naproxen and decrease retention times. Separation was done in a Zorbax SB C8 column (250 × 4.6 mm, 5 μm) with a mobile phase containing acidic 0.007 M sodium dodecyl sulfate/acetonitrile (50:50, v/v) at a flow rate of 1 mL/min. Detection was performed with an excitation wavelength of 280 nm and emission of 310 nm and 360 nm for internal standard and Naproxen, respectively. The method was validated by International Conference of Harmonization standards. The method is specific, accurate, and precise (relative standard deviation <3%). Limits of detection and quantification were 0.08 and 0.25 μg/mL, respectively, for biological samples. This method was applied to analyze brain/plasma ratios in mice that had received oral administrations of Naproxen micellar formulations containing 10% w/w of sodium dodecyl sulfate, Cremophor RH 40, or Tween 80. The sodium dodecyl sulfate micelles were faster and more widely distributed in the mouse brains.