Patent ID: 8359164

Claim:
A method for determining an active drug concentration in pharmaceutical tablets or powders by using near infrared spectroscopy and supervised principal component analysis, said method comprising the steps of: a. designing a plurality of calibration samples with variations in drug concentration, and introducing additional systematic variations by changing the composition of said calibration samples, including changing the composition of excipients, and by changing physical properties of said calibration samples, including changing tablet hardness; b. performing spectral pretreatment of acquired near infrared (NIR) spectra without using multiplicative scattering correction (MSC) or extended multiplicative scattering correction (EMSC), and then selecting a wavelength range/region from the spectra to produce data matrix X 1 ; c. performing Supervised Principal Component Analysis (SPCA) to decompose matrix X 1 in order to obtain a loading matrix P 1 and a score matrix T 1 ; d. determining the correlation between the Supervised Principal Component (PC) scores and nominal drug concentration; e. examining orthogonality of the Supervised Principal Component (PC) scores of desired latent variables in a two-dimensional Principal Component (PC) space, wherein said desired latent variables are the ones that describe the variations of drug concentration in the calibration samples; f. evaluating said desired latent variables to determine three criteria: 1) the orthogonality among latent variables is genuine, 2) there is a correlation between a plot of the loading matrix and the NIR spectrum of a chemical entity of interest, and 3) there is a linear relationship between the scores of said latent variables and nominal drug concentration values; g. if said three criteria are satisfied, going to step h, if said three criteria are not satisfied, choosing different wavelength ranges and repeating step b, to step f, with new data matrix X 2 , X 3 . . . X n , new loading matrix P 2 , P 3 . . . P n , and new score matrix T 2 , T 3 . . . T n , until said three criteria are satisfied, then going to step h; h. performing spectral pretreatment of acquired NIR spectra from unknown samples; i. combining the spectra sets of said unknown samples and said calibration samples; j. truncating said combined spectra according to the wavelength range determined by steps b, to g, to generate a prediction matrix X p ; k. performing a Supervised Principal Component Analysis (PCA) with prediction matrix X p to obtain a loading matrix P p and a score matrix T p ; and l. calculating drug content in unknown samples based on said score matrix T p obtained from said prediction matrix X p .