title: The use of FT-NIR for API content assay in organic solvent media: a single calibration for multiple downstream processing streams.
abstract: The use of near infrared spectroscopy (NIRS) in downstream solvent based processing steps of an active pharmaceutical ingredient (API) is reported. A single quantitative method was developed for API content assessment in the organic phase of a liquid-liquid extraction process and in multiple process streams of subsequent concentration and depuration steps. A new methodology based in spectra combinations and variable selection by genetic algorithm was used with an effective improvement in calibration model prediction ability. Root mean standard error of prediction (RMSEP) of 0.05 in the range of 0.20-3.00% (w/w) was achieved. With this method, it is possible to balance the calibration data set with spectra of desired concentrations, whenever acquisition of new spectra is no longer possible or improvements in model's accuracy for a specific selected range are necessary. The inclusion of artificial spectra prior to genetic algorithms use improved RMSEP by 10%. This method gave a relative RMSEP improvement of 46% compared with a standard PLS of full spectral length.
authors.affiliation: IBB, Centre for Biological and Chemical Engineering, IST, Technical University of Lisbon, Avenue Rovisco Pais, P-1049-001 Lisbon, Portugal. bsel@ist.utl.pt
authors.forename: Licínia O
authors.initials: LO
authors.lastname: Rodrigues
authors.forename: Joaquim P
authors.initials: JP
authors.lastname: Cardoso
authors.forename: José C
authors.initials: JC
authors.lastname: Menezes
mesh_terms: D000465:Algorithms; D001681:Biological Assay / Q000379:methods*; D002138:Calibration; D009930:Organic Chemicals / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D012996:Solutions; D012997:Solvents