DEVELOPMENT OF MULTIPLE SAMPLE SOLID-STATE NMR PROBES FOR ANALYSIS OF PHARMACEUTICAL COMPOUNDS AND FORMULATIONS

Abstract

Solid-state NMR spectroscopy (ssNMR) is an extremely powerful technique for the analysis of pharmaceutical dosage forms. A major limitation of ssNMR is the number of samples that can be analyzed in a given period of time. Development of three versions of probes that contain multiple magic angle spinning (MAS) modules for interleaved acquisition has been done, and each shows no loss in spectral quality compared to a standard probe. A prototype probe incorporating two MAS modules was first developed. This version is limited to being a two-module probe due to the large amounts of space required for the tuning elements, which are located next to the MAS modules. A new probe design incorporating coaxial transmission lines and smaller MAS modules has also been constructed. This probe allows for close proximity of the MAS modules (within 3 cm) and the capability of remote tuning and sample changing. This probe design can be easily scaled to incorporate more than two MAS modules, which is a limitation of the previous design. The number of modules that can be incorporated is only limited by the number of transmission lines that will fit in a cross-sectional diameter of the bore and the axial field length of the magnet. A third version addresses the main issues of length and linear actuation that the first generation probes have. So that the superconducting magnet can be left at "factory" height, a non-actuated probe that has the ability to collect two samples at a time has been constructed and tested. The radio frequency circuits have been isolated to such a degree that they do not dramatically affect the spectra of one another. Spectra of ssNMR standards: methylglutaric acid, hexamethylbenzene, and adamantane were acquired to show comparable performance of all multiple sample probe versions and conventional probes.