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Visualization and measurement of drugs themselves as well as biological responses to those drugs are crucial in pharmacological research. To this end, various fluorescent dyes and proteins have been developed. Despite such progresses, there still remains technical difficulties to overcome in bioimaging that keep many pharmacological targets and phenomena invisible. Outside the fields of biology where fluorescence and luminescence prevail, variety of other optical phenomena are well known and utilized. These optical phenomena can shed unique lights on biological phenomena based on their specific physical and chemical properties. Although applications of these optical phenomena to biology are yet to be explored, they have high potentials in realizing visualization and measurement of currently invisible targets and phenomena, and thereby bringing new insights into pharmacological research. Thus, here I will introduce Raman scattering microscopy that visualize vibration of functional groups as an alternative imaging platform to fluorescence and luminescence. Special focus will be put on two recent technical advancements; namely, nonlinear Raman scattering microscopy that utilizes multi-photon effect of highly tissue penetrating near-infrared lights, and Raman-tag that realizes tagging of targets that could not have been labeled, combination of which is expected to pave a way toward imaging previously invisible targets in pharmacology.

The feasibility of a simple Fourier transform (FT)-Raman spectroscopic method for the quantitative determination of unexpected active drug polymorphs or amorphous in drug products was explored. In this study, calibration samples were prepared by physically mixing drug substances with their polymorphs or amorphous, without using excipients. A partial least-squares (PLS) method was applied to the quantitative analysis of the FT-Raman spectra obtained. As model drug products, compound A drug substances (form alpha) containing several ratios of polymorph, (form beta), were physically mixed with excipients to prepare powder samples corresponding to compound A tablets (30 and 120 mg). The mixture of compound B, form I and amorphous, were also mixed with excipients to mimic powdered compound B tablets (32 mg). Satisfactory relationships between the theoretical contents of polymorph or amorphous and determined contents were obtained; quantitation limits were 5-10%. In the case of powder samples corresponding to compound A tablets (30 mg) and compound B tablets (32 mg), differentiating the FT-Raman spectra prior to PLS analysis was required to improve the precision of the determinations.