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Jenifer Mains, Clive Wilson, Andrew Urquhart; The Impact Of Chemical Structure On The Use Of Tof-sims To Investigate Drug Distribution. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4640.
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The use of of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to investigate the ocular drug distribution of two probe drug molecules.
Intravitreal injections of Amitriptyline hydrochloride and Dexamethasone sodium phosphate were administrated to perfused and non-perfused ovine eyes. The vitreous humor, the lens, and the retina of the eyes were then removed and divided into front, middle, and back sections. ToF-SIMS analysis was performed on each cross- section of the vitreous humor using Bi3+cluster source and used to map drug distribution.
The utility of ToF-SIMS to map drug distribution is dependent on the uniqueness of the chemical structure amongst natural components. Amitripyline has a complex heterocyclic structure without covalently-bonded halogens and was more difficult to fingerprint, therefore principal component analysis (PCA) was employed in order to measure the distribution of the model drug. For dexamethasone the method was more sensitive due to the fluorine moiety present in the drug structure. In the positive ion spectra, four key drug fragment peaks were identified and in the negative ion spectra, one key drug peak was imaged. Differences in distribution were demonstrated between the non-living the living eye. Figure 1 details the front, the middle and the back section of each tissue and shows that dexamethasone diffused slowly through the vitreous in the non-perfused eye (A) however, when perfused (B), distribution in the vitreous was faster and the drug was shown to penetrate into the posterior retina and the lens.
The results illustrate the facility of ToF-SIMS in defining spatial characteristics of drug distribution within ocular tissues. The specificity and sensitivity is dependent on the availability of a drug molecule with ‘non-biological’ characteristics. Moreover, differences in drug movement through the vitreous humor elicited by perfusion in the ovine eye were demonstrated, and illustrate the importance of convective flow as a determinant of distribution.
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