Near-infrared spectrometry for the quantification of dermal absorption of econazole nitrate and 4-cyanophenol.
OBJECTIVE
The purpose of this study was to demonstrate the utility of near-infrared (NIR) spectroscopy for the in vitro quantification of econazole nitrate (EN) and 4-cyanophenol (4-CP) in hairless guinea pig skin.


METHODS
NIR spectra were collected from each of the following: EN and 4-CP powders, EN and 4-CP in solution, and skin samples following topical exposure to either 4-CP in water or EN in propylene glycol and topical creams. To predict drug concentration from NIR spectra, principal component regression (PCR), interval PCR, and uninformative variable elimination PCR were each used with a leave-one-out cross-validation, and results were compared. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts.


RESULTS
NIR results matched the HPLC results for the quantification of 4-CP and EN in skin exposed to saturated solutions and topical creams with an r2 > 0.90, a standard error of estimation < 7.0%, and a standard error of performance < 8.0%.


CONCLUSIONS
This experiment demonstrated that NIR closely parallels results obtained from tissue extraction and HPLC analysis, proving its potential utility for the rapid and noninvasive determination of topical bioavailability/bioequivalence of EN and quantification of the model chemical 4-CP. Investigation of drugs in human skin is now justified.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 725 Rose Street, Lexington, KY 40536-0082, USA.
Joseph
J
Medendorp
Jhansi
J
Yedluri
Dana C
DC
Hammell
Tao
T
Ji
Robert A
RA
Lodder
Audra L
AL
Stinchcomb
D000465:Algorithms; D000818:Animals; D000935:Antifungal Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004464:Econazole / Q000032:analysis* / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009824:Ointments; D019999:Pharmaceutical Solutions; D011208:Powders; D025341:Principal Component Analysis; D012869:Skin Absorption; D019265:Spectroscopy, Near-Infrared
D000935:Antifungal Agents; D007202:Indicators and Reagents; D009824:Ointments; D019999:Pharmaceutical Solutions; D011208:Powders; D004464:Econazole