Advanced Calibration Strategy for in Situ Quantitative Monitoring of Phase Transition Processes in Suspensions Using FT-Raman Spectroscopy

There is an increasing interest in using Raman spectroscopy to identify polymorphic forms and monitor phase changes in pharmaceutical products for quality control. Compared with other analytical techniques for the identification of polymorphs such as X-ray powder diffractometry and infrared spectros...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2008-09, Vol.80 (17), p.6658-6665
Main Authors: Chen, Zeng-Ping, Fevotte, Gilles, Caillet, Alexandre, Littlejohn, David, Morris, Julian
Format: Article
Language:English
Subjects:
Analytical chemistry
Calibration
Chemical and Process Engineering
Chemistry
Crystallization
Engineering Sciences
Exact sciences and technology
Fourier Analysis
Particle Size
Phase Transition
Phase transitions
Sensitivity and Specificity
Solvents - chemistry
Spectrometric and optical methods
Spectrum analysis
Spectrum Analysis, Raman - methods
Suspensions
Time Factors
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Summary:There is an increasing interest in using Raman spectroscopy to identify polymorphic forms and monitor phase changes in pharmaceutical products for quality control. Compared with other analytical techniques for the identification of polymorphs such as X-ray powder diffractometry and infrared spectroscopy, FT-Raman spectroscopy has the advantages of enabling fast, in situ, and nondestructive measurements of complex systems such as suspension samples. However, for suspension samples, Raman intensities depend on the analyte concentrations as well as the particle size, overall solid content, and homogeneity of the solid phase in the mixtures, which makes quantitative Raman analysis rather difficult. In this contribution, an advanced model has been derived to explicitly account for the confounding effects of a sample’s physical properties on Raman intensities. On the basis of this model, a unique calibration strategy called multiplicative effects correction (MEC) was proposed to separate the Raman contributions due to changes in analyte concentration from those caused by the multiplicative confounding effects of the sample’s physical properties. MEC has been applied to predict the anhydrate concentrations from in situ FT-Raman measurements made during the crystallization and phase transition processes of citric acid in water. The experimental results show that MEC can effectively correct for the confounding effects of the particle size and overall solid content of the solid phase on Raman intensities and, therefore, provide much more accurate in situ quantitative predictions of anhydrate concentration during crystallization and phase transition processes than traditional PLS calibration methods.
ISSN:0003-2700
1520-6882
DOI:10.1021/ac800987m