RESUMO
A new methodology, matrix-enhanced secondary ion mass spectrometry (ME-SIMS), is reported for the molecular analysis of biomaterials. The technique applies static secondary ion mass spectrometry (SSIMS) techniques to samples prepared in a solid organic matrix similar to sample preparations used in matrix-assisted laser desorption/ionization (MALDI). Molecular ions are observed in this ion beam sputtering of organic mixtures for peptides and oligonucleotides up to masses on the order of 10 000 Da. This matrix-enhanced SIMS exhibits substantial increases in the ionization efficiency of selected analyte molecules compared to conventional SSIMS processes. Thus, higher mass peptides, proteins, and nucleic acids become accessible to near-surface analysis by ion beam techniques, and subpicomole sensitivity has been demonstrated. A number of matrices were examined for their efficiency in ME-SIMS applications, and these initial matrix studies focused on common MALDI matrices and their isomers. The results of this survey indicate that 2,5-dihydroxybenzoic acid provides the best general enhancement of molecular secondary ions emitted from analyte/matrix mixtures.
RESUMO
The localization of a peptide drug dispersed in a solid matrix of hydroxypropyl cellulose (HPC) was determined at micrometer lateral resolution using secondary ion mass spectrometry (SIMS)/ion microscopy. Leuprolide formulated as a sustained release drug delivery device has been selected as a model compound for this investigation. One key facet of this study was to attempt to understand the distribution and ultimate bioavailability of the peptide dispersed in an inert polymer matrix. The results reported in this paper demonstrate that the lateral distribution of leuprolide along the surfaces of cross sections prepared from different polymer formulations is different. Ion microscopy directly measures the lateral distribution of protonated molecular ions as well as specific fragment peaks and provides a direct method of determining peptide distributions in polymers. Ion images of leuprolide dispersed in HPC demonstrate that the peptide distribution is critically dependent on polymer composition. The mass spectrometry results augment quantitative X-ray photoelectron (XPS) measurement of C and N levels in different polymer/peptide formulations. The combination of XPS and TOF-SIMS techniques provides a powerful method for determining the distribution of peptides in polymer matrices.