Axially slanted laser illumination scheme for direct and accurate Raman spectroscopic determination of gemcitabine concentration in freeze-dried gemcitabine injection powder housed in a glass container.

When Raman spectroscopy is employed for a direct in situ determination of ingredient concentration for a product stored in a glass container, minimization of the interfering glass background in the collected spectrum is demanding to secure a more accurate analysis. To meet this request, an axially slanted illumination (ASI) scheme slantingly irradiating laser on the headspace side of a glass container and positioning a detector beneath the container was demonstrated in this study. This ASI scheme was basically designed to increase the distance between the laser illumination spot and detector location to minimize the number of glass photons reaching the detector. The analytical utility of the scheme was evaluated for the determination of gemcitabine concentration (42.9-58.2 wt%) in the gemcitabine injection powder housed in a glass container. Using the ASI scheme, the spectral features of the gemcitabine powder became distinct with only a weak underlying glass background signal. For comparative purpose, when an axially perpendicular offset (APO) scheme perpendicularly irradiating laser on the side wall where the sample was filled was used, the magnitude of glass background was higher, and the most intense gemcitabine peak was largely buried in the glass peak. The accuracy for determination of gemcitabine concentration using the ASI scheme was superior with an error of 0.20 wt%, while 0.33 wt% with employing the APO scheme. Overall, this study demonstrates that the ASI scheme is a potentially versatile Raman spectroscopic tool for fast non-sampling analysis of other products stored in a glass container.