Low-level determination of polymorph composition in physical mixtures by near-infrared reflectance spectroscopy

Near-infrared reflectance spectroscopy (NIRS) was employed to quantify sulf athiazole (STZ) forms I and III in binary physical mixtures in which one fo rm was the dominant component. Physical mixtures of the polymorph pair were made by weight, ranging from 0 to 5% STZ form I mixed with STZ form III, a nd near-infrared spectra of the powder samples contained in glass vials wer e obtained over the wavelength region of 1100 to 2500 nm. A calibration plo t was constructed by plotting STZ form I weight percent against a ratio of second-derivative values of log (1/R') (where R' is the relative reflectanc e) versus wavelength. The coefficients of determination, R-2, were > 0.9983 and standard errors were low for these calibration models. The instrument reproducibility, method error, and limits of detection (LOD) and quantifica tion (LOQ) of the method were assessed. The LOD and LOQ were determined fro m the standard deviation of the response of the 0% analyte sample (0% STZ f orm I containing 100% STZ form III). The LOQ was subsequently validated wit h independently prepared samples. The results show that polymorphs can be q uantified in binary physical mixtures in the 0.3% polymorph composition ran ge. These studies indicate that NIRS is a precise and accurate quantitative tool for determination of polymorphs in the solid state, is comparable to other characterization techniques, and is more convenient to use than many other methods. (C) 2001 Wiley-Liss, Inc.