Purpose: The purpose of this study was to demonstrate the use of near-infrared (NIR) spectrometry for the in vitro quantification of econazole nitrate (EN) and estradiol (EST) in human skin.
Methods: NIR spectra were collected from EN and EST powders to verify the presence of NIR chromophores. One percent EN cream, a saturated solution of EN, or 0.25% EST solution was applied to human skin. NIR spectra were collected and one-point net analyte signal (NAS) multivariate calibration was used to predict the drug concentrations. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts.
Results: NIR spectroscopy measured dermal absorption from saturated solutions of EN on human skin with an r2=0.990, standard error of estimation (SEE)=2.46%, and a standard error of performance (SEP)=3.55%, EN cream on skin with an r2=0.987, SEE=2.30%, and SEP=2.66%, and 0.25% solutions of EST on skin with an r2=0.987, SEE=3.30%, and SEP=5.66%. Despite low permeation amounts of both drugs through the stratum corneum into human tissue, the NIR signal-to-noise ratio was greater than three, even for the lowest concentrations.
Conclusion: NIR analyses paralleled the results obtained from HPLC, and thus could serve as a viable alternative for measuring the topical bioavailability/bioequivalence of different EN and EST formulations. Because these experiments were conducted in human tissue, this research suggests an all-optical in vivo method of measurement for dermal absorption could be developed.