Validation of Reflectance Infrared Spectroscopy as a Quantitative Method to Measure Percutaneous Absorption In Vivo

Naruhito Higo, Aarti Naik, D. Bommi Bommannan, Russell O. Potts, Richard H. Guy

Research output: Contribution to journalArticlepeer-review


Attenuated total-reflectance infrared (ATR-IR) spectroscopy has been used 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 propylene glycol or (b) in an identical vehicle which also contained 5% (v/v) oleic (cis-9-octadecenoic) acid. At the end of the treatment periods, SC at the application site was progressively removed by adhesive tape-stripping. Prior to the removal of the first tape-strip, and after 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 absorbance at 2230 cm−1. The absolute amount of CP, as a function of SC depth, was determined by "spiking” the applied solutions with 14C-labeled compound and subsequent liquid scintillation counting of the removed tape-strips. The presence of oleic acid in the applied formulation significantly increased the rate and extent of CP delivery as evaluated by either spectroscopy or radiochemical analysis. Furthermore, the ATR-IR and direct 14C analysis of CP as a function of SC position were highly correlated. These data strongly support, therefore, the validation of ATR-IR as a quantitative tool to assess percutaneous penetration in vivo.

Original languageEnglish
Pages (from-to)1500-1506
Number of pages7
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Issue number10
Publication statusPublished - 31 Oct 1993


  • 4-cyanophenol
  • infrared spectroscopy
  • oleic acid
  • penetration enhancement
  • skin penetration
  • transdermal delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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