title: Multivariate figures of merit (FOM) investigation on the effect of instrument parameters on a Fourier transform-near infrared spectroscopy (FT-NIRS) based content uniformity method on core tablets.
abstract: Since near infrared spectroscopy (NIRS) was introduced to the pharmaceutical industry, efforts have been spent to leverage the power of chemometrics to extract out the best possible signal to correlate with the analyte of the interest. In contrast, only a few studies addressed the potential impact of instrument parameters, such as resolution and co-adds (i.e., the number of averaged replicate spectra), on the method performance of error statistics. In this study, a holistic approach was used to evaluate the effect of the instrument parameters of a FT-NIR spectrometer on the performance of a content uniformity method with respect to a list of figures of merit. The figures of merit included error statistics, signal-to-noise ratio (S/N), sensitivity, analytical sensitivity, effective resolution, selectivity, limit of detection (LOD), and noise. A Bruker MPA FT-NIR spectrometer was used for the investigation of an experimental design in terms of resolution (4 cm(-1) and 32 cm(-1)) and co-adds (256 and 16) plus a center point at 8 cm(-1) and 32 co-adds. Given the balance among underlying chemistry, instrument parameters, chemometrics, and measurement time, 8 cm(-1) and 32 co-adds in combination with appropriate 2nd derivative preprocessing was found to fit best for the intended purpose as a content uniformity method. The considerations for optimizing both instrument parameters and chemometrics were proposed and discussed in order to maximize the method performance for its intended purpose for future NIRS method development in R&D.
authors.affiliation: SMDD, Lilly Research Laboratories, Indianapolis, IN 46285, United States.
authors.forename: Greg D
authors.initials: GD
authors.lastname: Doddridge
authors.affiliation: SMDD, Lilly Research Laboratories, Indianapolis, IN 46285, United States. Electronic address: shi_zhenqi@lilly.com.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Shi
mesh_terms: D005583:Fourier Analysis; D057230:Limit of Detection; D015999:Multivariate Analysis; D015203:Reproducibility of Results; D059629:Signal-To-Noise Ratio; D019265:Spectroscopy, Near-Infrared / Q000379:methods / Q000592:standards*; D013607:Tablets / Q000032:analysis* / Q000592:standards*
chemical_list: D013607:Tablets
keywords: Content uniformity; Method characterization; Multivariate figures of merit; Near infrared spectroscopy; Process Analytical Technology