VALIDATION OF REFLECTANCE INFRARED-SPECTROSCOPY AS A QUANTITATIVE METHOD TO MEASURE PERCUTANEOUS-ABSORPTION IN-VIVO

Attenuated total-reflectance infrared (ATR-IR) spectroscopy has been u sed to follow the penetration of a model compound (4-cyanophenol; CP) across human stratum corneum (SC) in vivo, in man. CP was administered for periods of 1, 2, or 3 hr, either (a) as a 10% (w/v) solution in p ropylene glycol or (b) in an identical vehicle which also contained 5% (v/v) oleic (cis-9-octadecenoic) acid. At the end of the treatment pe riods, SC at the application site was progressively removed by adhesiv e tape-stripping. Prior to the removal of the first tape-strip, and af ter each subsequent tape-strip, an ATR-IR spectrum of the treated site was recorded. The presence of CP, as a function of position in the SC , was monitored spectroscopically via the intense C=N stretching absor bance at 2230 cm-1. The absolute amount of CP, as a function of SC dep th, was determined by ''spiking'' the applied solutions with C-14-labe led compound and subsequent liquid scintillation counting of the remov ed tape-strips. The presence of oleic acid in the applied formulation significantly increased the rate and extent of CP delivery as evaluate d by either spectroscopy or radiochemical analysis. Furthermore, the A TR-IR and direct C-14 analysis of CP as a function of SC position were highly correlated. These data strongly support, therefore, the valida tion of ATR-IR as a quantitative tool to assess percutaneous penetrati on in vivo.