ToF-SIMS analysis of ocular tissues reveals biochemical differentiation and drug distribution

Eur J Pharm Biopharm. 2011 Oct;79(2):328-33. doi: 10.1016/j.ejpb.2011.04.006. Epub 2011 Apr 21.

Abstract

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to obtain mass spectra from three ocular tissues, the lens, the vitreous and the retina. All three tissues were extracted from control ovine eyes and ovine eyes treated with model drug. To identify variations in surface biochemistry of each ocular tissue, principal component analysis (PCA) was applied to ToF-SIMS data. Interesting physiological differences in Na(+) and K(+) distribution were shown across the three tissue types, with other elements including Ca(2+) and Fe(2+) distribution also detected. In addition to the identification of small molecules and smaller molecular fragments, larger molecules such as phosphocholine were also detected. The ToF-SIMS data were also used to identify the presence of a model drug compound (amitriptyline--chosen as a generic drug structure) within all three ocular tissues, with model drug detected predominantly across the vitreous tissue samples. This study demonstrates that PCA can be successfully applied to ToF-SIMS data from different ocular tissues and highlights the potential of coupling multivariate statistics with surface analytical techniques to gain a greater understanding of the biochemical composition of tissues and the distribution of pharmaceutically active small molecules within these tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eye / chemistry*
  • Eye / metabolism*
  • Lens, Crystalline / chemistry
  • Lens, Crystalline / metabolism
  • Multivariate Analysis
  • Pharmacokinetics
  • Principal Component Analysis / methods*
  • Retina / chemistry
  • Retina / metabolism
  • Sheep
  • Spectrometry, Mass, Secondary Ion / methods*
  • Tissue Distribution
  • Vitreous Body / chemistry
  • Vitreous Body / metabolism