It depends on the solubility of the molecule in water, methanol, or acetonitrile; which are the common constituents of mobile phases In reversed phase cromatography, which I assume you intend to use. If the molecule has a reported refraction index then the detector you suggest might work.
If an RI detector is used, the mobile phase mode must be isocratic (50/50 ACN/water?). The sample would also have to be a 'neat' sample since the RI detector is very insensitive.