This work proposes a novel chemometric methodology for in-line near infrared spectroscopy (NIRS) monitoring of pharmaceutical powder moisture in a fluidised-bed dryer. The collected spectra are analysed by multivariate chemometrics involving the preparation of numerous laboratory samples. A different methodology, using only plant samples, was tested in real-time. A specially designed probe tip, allowing for robust in-situ spectral acquisition, was designed. The results prove that NIRS can be as efficient as traditional quality analyses, e.g. loss-on-drying, in measuring powder moisture content in a fluidised bed dryer with a calibration model based only on plant samples. (c) 2011 Canadian Society for Chemical Engineering