Quantifying crystal form content in physical mixtures of (+/-)-tartaric acid and (+)-tartaric acid using near infrared reflectance spectroscopy.

The objective of this study was to use diffuse reflectance near infrared spectroscopy (NIRS) to determine racemic compound content in physical mixtures composed primarily of the enantiomorph and to assess the error, instrument reproducibility and limits of detection (LOD) and quantification (LOQ) of the method. Physical mixtures ranging from 0 to 25% (+/-)-tartaric acid in (+)-tartaric acid were prepared and spectra of the powder samples contained in glass vials were obtained using a Foss NIRSystems Model 5000 monochrometer equipped with a Rapid Content Analyzer scanning from 1100 to 2500 nm. A calibration curve was constructed by plotting (+/-)-tartaric acid weight percent against the 2(nd) derivative values of log (1/R) vs lambda at a single wavelength, normalized with a denominator wavelength (1480 nm/1280 nm). Excellent linearity was observed (R(2)=0.9999). The standard error of calibration (SEC) was 0.07 and the standard error of prediction (SEP) for the validation set was 0.11. Instrument and method errors for samples in the 2% composition range ((+/-)-tartaric acid in (+)-tartaric acid) were less than 1% RSD and 3% RSD, respectively. The practical LOD and LOQ were 0.1% and 0.5%, respectively, and comparable to the calculated LOD and LOQ. These studies show that NIRS can be used as a rapid and sensitive quantitative method for determining racemate content in the presence of the enatiomerically pure crystal in the solid-state.