GAS-CHROMATOGRAPHY AS A REFERENCE METHOD FOR MOISTURE DETERMINATION BY NEAR-INFRARED SPECTROSCOPY

Near-infrared spectroscopic (MIRS) methods were developed to determine moisture in freeze-dried drug products with gas chromatography as the reference measurement. The gas chromatography method was optimized to provide a relative standard deviation of 1.1%, Because NIRS calibrati on models are limited by the quality of the reference measurement, all aspects of the GC technique were studied, including water standard pr eparation, operating conditions, and sample treatment. Vials of a free ze-dried drug product were prepared with water contents from 0.1 to 5. 7% (w/w). NIR spectra were collected over the spectral range of 1100-2 500 nm for these vials. Calibration models were established from these spectra by PLS regression analysis. Second-derivative spectra were us ed and spectral range and number of PLS factors were optimized for the lowest standard error of prediction (SEP). The best calibration was b uilt with second-derivative spectra in the spectral range of 1850-1960 nm with three PLS factors acid provided a SEP of 0.07% water (w/w). T hese results indicate that GC is a competitive reference method and th at NIRS can be used for water determination in cases where other moist ure analysis techniques are not compatible.