Raman imaging of pharmaceutical materials: refractive index effects on contrast at buried interfaces.

Resolution targets composed of bilayer polydimethylsiloxane (PDMS) devices with buried polyethylene glycol (PEG) channels have been fabricated using traditional photolithographic and micromolding techniques to develop resolution targets that mimic pharmaceutical materials. Raman chemical images of the resulting PEG-in-PDMS devices composed of varying parallel line widths were investigated by imaging the PEG lines through a thin overlayer of PDMS. Additionally, a scattering agent, Al2O3, was introduced at varying concentrations to each layer of the device to explore the effects of scattering materials on Raman images. Features in the resulting chemical images of the PEG lines suggest that reflection at the PEG/PDMS interface contributes to the Raman signal. A model based on geometric optics was developed to simulate the observed image functions of the targets. The results emphasize the influence of refractive index discontinuities at the PEG/PDMS interface on the apparent size and shape of the PEG features. Such findings have an impact on interpretation of Raman images of nonabsorbing, opaque pharmaceutical samples.

Rapid screening and structural elucidation of a novel sibutramine analogue in a weight loss supplement: 11-desisobutyl-11-benzylsibutramine.

A novel analogue of sibutramine, 11-desisobutyl-11-benzylsibutramine, has been discovered. During routine ion mobility spectrometry (IMS) screening of a weight loss supplement collected at an US FDA import operation facility an unknown peak was observed. Further analysis of the supplement by liquid chromatography-mass spectrometry (LC-MS) and high resolution mass spectrometry revealed an unknown peak with a relative retention time of 1.04 with respect to sibutramine and a predicted formula of C20H24NCl. In order to elucidate the analogue's structure, it was isolated from the supplement and characterized by tandem mass spectrometry and nuclear magnetic resonance (NMR), which revealed the analogue possessed a benzyl moiety at the 11 position in place of the isobutyl group associated with sibutramine.

Qualitative screening for adulterants in weight-loss supplements by ion mobility spectrometry.

Ion mobility spectrometry (IMS) served as a rapid, qualitative screening tool for the analysis of adulterated weight-loss products. We have previously shown that sibutramine extracted into methanol from dietary supplements can be detected at low levels (2ng) using a portable IMS spectrometer, and have adapted a similar method for the analysis of additional weight-loss product adulterants. An FDA collaborative study helped to define the limits for fluoxetine with a limit of detection of 2ng. We also evaluated more readily available, less toxic extraction solvents and found isopropanol and water were comparable to methanol. Isopropanol was favored over water for two reasons: (1) water increases the analysis time and (2) aqueous solutions were more susceptible to pH change, which affected the detection of sibutramine. In addition to sibutamine and fluoxetine, we surveyed 11 weight-loss adulterants; bumetanide, fenfluramine, furosemide, orlistat, phenolphthalein, phentermine, phenytoin, rimonabant, sertraline and two sibutramine analogs, desmethylsibutramine and didesmethylsibutramine, using portable and benchtop ion mobility spectrometers. Out of these 13 active pharmaceutical ingredients (APIs), portable and benchtop ion mobility spectrometers were capable of screening products for 10 of these APIs. The developed procedure was applied to two weight-loss dietary supplements using both portable and benchtop instruments. One product contained didesmethylsibutramine while the other contained didesmethylsibutramine and phenolphthalein.