Purpose: To determine naproxen levels in human plasma using a new liquid chromatography-Mass spectroscopy/Mass spectroscopy (LC-MS/MS) method that involves a simple and single step extraction procedure using low-cost reagents.

Method: A novel liquid chromatography–tandem mass spectrometry method for the quantitative determination of naproxen in human K2-EDTA plasma in negative ion mode was employed and validated using zidovudine as internal standard (IS). Sample preparation was accomplished by liquid-liquid extraction technique. The eluted samples were chromatographed on Zorbax Eclipse XDB phenyl 4.6 × 75 mm, 3.5 µm column (Agilent Technologies) using a mobile phase consisting of acetonitrile: 20 mM ammonium acetate (90:10 v/v).The injection volume was 15 µL  and the total run time was 3.0 min. The method was validated for all parameters for naproxen.

Results: The method showed selectivity and linearity over a concentration range of 500.1 ng/mL to 100028.5 ng/mL The validation data indicate precision and accuracy of 90 - 110 % and < 15 %), respectively, as well as recovery (80.63 %), stability (mostly stable) and carryover (0 %).

Conclusion: A rapid and selective LC-MS/MS method for the quantification of naproxen in human plasma has been developed and can be used in therapeutic drug monitoring of this drug as well as in bioequivalence studies of the drug.