Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound

A pharmaceutical active compound H appears in two polymorphs, A and B, that are stable below and above room temperature, respectively. The A- and B-forms were found to have distinct FT-Raman spectra, in particular for a band at 1716 cm-1 (A-form) or 1724 cm-1 (B-form). Mixtures of A- in B-form were prepared, and the relative intensity of the characteristic bands at 1716 and 1724 cm-1 was found to be proportional to the relative amounts of A- and B-form in the mixtures. A calibration was made which was linear in the range from 1.8 to 15.4% (w/w) of A- in B-form. The results were compared with other methods for analysis of polymorphs: FT-IR spectrometry, differential scanning calorimetry, and powder X-ray diffractometry. A novel FT-Raman sample presentation method for inhomogeneous samples is presented.