Fourier transform Raman spectroscopy of thin films

Conventional Raman measurements of dyes in the visible region exhibit resonant effects which enhance the Raman scattering cross-section of the chromophores by several orders of magnitude but make scattering from other parts of the molecules, such as the hydrocarbon chains, unobservable. Taking advantage of the benefits inherent to Fourier transform (FT) spectroscopy, Raman spectra can now be measured routinely with an FT IR spectrometer and a continuous wave Nd:YAG laser. By coupling the laser excitation into a thin film waveguide, we have recently observed FT Raman spectra of a thin film of polystyrene. The advantages of using integrated optics with FT Raman spectroscopy for Langmuir-Blodgett films of dye molecules are also discussed.     

Quantitative transmission Raman spectroscopy of pharmaceutical tablets and capsules

Quantitative analysis of pharmaceutical formulations using the new approach of transmission Raman spectroscopy has been investigated. For comparison, measurements were also made in conventional backscatter mode. The experimental setup consisted of a Raman probe-based spectrometer with 785 nm excitation for measurements in backscatter mode. In transmission mode the same system was used to detect the Raman scattered light, while an external diode laser of the same type was used as excitation source. Quantitative partial least squares models were developed for both measurement modes. The results for tablets show that the prediction error for an independent test set was lower for the transmission measurements with a relative root mean square error of about 2.2% as compared with 2.9% for the backscatter mode. Furthermore, the models were simpler in the transmission case, for which only a single partial least squares (PLS) component was required to explain the variation. The main reason for the improvement using the transmission mode is a more representative sampling of the tablets compared with the backscatter mode. Capsules containing mixtures of pharmaceutical powders were also assessed by transmission only. The quantitative results for the capsules' contents were good, with a prediction error of 3.6% w/w for an independent test set. The advantage of transmission Raman over backscatter Raman spectroscopy has been demonstrated for quantitative analysis of pharmaceutical formulations, and the prospects for reliable, lean calibrations for pharmaceutical analysis is discussed.     

Transmission fourier transform Raman spectroscopy of pharmaceutical tablet cores

Transmission Fourier transform (FT) Raman spectroscopy of pharmaceutical tablet cores is demonstrated using traditional, unmodified commercial instrumentation. The benefits of improved precision over backscattering Raman spectroscopy due to increased sample volume are demonstrated. Self-absorption effects on analyte band ratios and sample probe volume are apparent, however. A survey of near-infrared (NIR) absorption spectra in the FT-Raman spectral range (approximately 0 to 3500 wavenumber shift from 1064 nm, or 1064 to 1700 nm) of molecules with a wide range of NIR-active functional groups shows that although absorption at the laser wavelength (1064 nm) is relatively small, some regions of the Raman spectrum coincide with NIR absorbances of 0.5 per cm or greater. Fortunately, the pharmaceutically important regions of the Raman shift spectrum from 0 to 600 cm(-1) and from 1400 to 1900 cm(-1) exhibit low self-absorption for most organic materials. A statistical analysis of transmission FT-Raman noise in spectra collected from different regions of a pharmaceutical tablet provides insight into both spectral distortion and reduced sampling volume caused by self-absorption.     

Quantitative nondestructive methods for the determination of ticlopidine in tablets using reflectance near-infrared and Fourier transform Raman spectroscopy

Two different nondestructive spectroscopy methods based on near-infrared (NIR) and Fourier transform (FT) Raman spectroscopy were developed for the determination of ticlopidine-hydrochloride (TCL) in pharmaceutical formulations and the results were compared to those obtained by high-performance liquid chromatography (HPLC). An NIR assay was performed by reflectance over the 850-1700 nm region using a partial least squares (PLS) prediction model, while the absolute FT-Raman intensity of TCL's most intense vibration was used for constructing the calibration curve. For both methodologies the spectra were obtained from the as-received film-coated tablets of TCL. The two quantitative techniques were built using five "manual compressed" tablets containing different concentrations and validated by evaluating the calibration model as well as the accuracy and precision. The models were applied to commercial preparations (Ticlid). The results were compared to those obtained from the application of HPLC using the methodology described by "Sanofi Research Department" and were found to be in excellent agreement, proving that NIR, using fiber-optic probes, and FT-Raman spectroscopy can be used for the fast and reliable determination of the major component in pharmaceutical analysis.     

Application of Fourier transform Raman spectroscopy for prediction of bitterness of peptides

The potential application of Fourier transform (FT) Raman spectroscopy to predict the bitterness of peptides was investigated. FT-Raman spectra were measured for the amino acid Phe and 9 synthetic di-, tri-, and tetra peptides composed of Phe, Gly, and Pro. Partial least squares regression (PLS)-1 analysis was applied to correlate the FT-Raman spectra with bitterness intensity values (R(caf) and log 1/T) reported in the literature. Using full cross-validation, Model 1 based on the single spectral data set for the nine peptides yielded a high correlation coefficient for calibration (R = 0.99), but a low correlation coefficient for prediction (R = 0.56). Two models were constructed using the data sets including replicate spectra for the calibrations and were validated using full cross-validation. Using leave-one-sample-set-out calibrations, Model 2, which was developed with the data for the peptides as well as Phe, yielded a low correlation coefficient (R = 0.533) for the prediction of the bitterness, while Model 3 developed with only the peptide data provided better correlation coefficients (R = 0.807 and 0.724 for R(caf) and log 1/T values, respectively). The correlation coefficients for prediction were 0.975 (R(caf) values) and 0.874 (log 1/T values) for Model 4, which was developed using subtracted spectral data (spectra of peptides with higher R(caf) values minus spectra of peptides with lower R(caf) values). Examination of the PLS regression coefficients at wavenumbers most highly correlated with bitterness revealed the importance of hydrophobicity and peptide length on bitterness. This study indicates the potential of FT-Raman spectroscopy as a useful tool for predicting bitterness of peptides and amino acids.     

Fourier transform Raman difference spectroscopy for detection of lignin oxidation products in thermomechanical pulp

Spruce thermomechanical pulp (TMP) was oxidized by the 2,2'azinobis-3-ethylbenzthiazoline-6-sulfonate cation radical (ABTS*+) in the presence and absence of oxygen. The pulp modification was monitored by Fourier transform (FT) Raman difference spectroscopy and other nondestructive spectroscopic methods. The ABTS*+ oxidative system resulted in modifications very similar to the laccase-ABTS-oxygen system, except for the FT-Raman results, which showed a difference in mechanisms attributed to a difference in produced Raman bands. Oxygen resulted in no oxygen-derived products, but only enhanced the production of a specific Raman band of several oxidation-produced bands. Detailed information on lignin reactions can be obtained from FT-Raman signals.     

Structural analysis of triacylglycerols and edible oils by near-infrared Fourier transform Raman spectroscopy

Fourier transform Raman spectroscopy was employed for structural analysis of triacylglycerols and edible oils. Raman spectra sensitively reflected structural changes in oils. Even slight structural fluctuation between triacylglycerols and free fatty acids led to obvious differences in Raman bands as shown by C-O-C stretching from 800 to 1000 cm(-1) and the band at 1742 cm(-1). Structural difference in geometric isomers was easily distinguished as proved by C = C stretching at 1655 cm(-1) (cis) shifting to 1668 cm(-1) (trans) and by =C-H in-plane bending at 1266 cm(-1) in cis disappearing in the trans isomer. Raman intensity at 1266, 1302, and 1655 cm(-1) changed concomitantly with the change of double-bond content in oils. It showed that FT-Raman was capable of precisly reflecting the content of double bonds in oils. A linear correlation with high consistency between the Raman intensity ratio (v1655/v1444) and the iodine value was obtained for commercial oils. Based on the results, FT-Raman spectroscopy proved itself a simple and rapid technique for oil analysis since each measurement could be directly completed in 3 min without any sample modifications.     

Internal standard in surface-enhanced Raman spectroscopy

A method is presented for the use of SAM layers as internal standards for calibration in surface-enhanced Raman spectroscopy. Three cyano-containing compounds were attached to gold colloids via a metal-sulfur bond and evaluated for spectral stability and normalization capacity. The results show that the analyte, rhodamine 6G, and the internal standard signal enhancement covaried, and it was possible to quantify the analyte with PLS. The fact that the enhancing substrate was chaotic assemblies with large variation in signal enhancement shows the versatility of this method.     

Fourier transform spectroscopy of LaS in the infrared

We recorded the emission spectrum of diatomic lanthanum sulfide on the Los Alamos Fourier transform spectrometer. In the region 7500-16,000 cm(-1), we identified over 120 bands and assigned them to the A(2)∏(r)-X(2)Σ(+) and B(2)Σ(+)-X(2)Σ(+) transitions. Each of these bands is four headed.     

Correction of instrument line-shape distortions in Fourier transform spectroscopy

A recovery procedure has been developed to correct instrument line-shape distortions observed in Fourier transform spectroscopy. The procedure can be described as a phase-error correction performed in the spectral domain to correct for path-difference-dependent phase errors observed in sharp spectral features. The technique has been applied successfully to high-resolution atmospheric emission spectra. The inherent broadening of the real features has been separated accurately from instrumental distortions. Using models for the path-difference-dependent error sources and data from two narrow window regions at 50 and 118 cm(-1), we show that the distortion has a simple dependence on the spectral frequency.     

Rapid, noninvasive quantitative determination of acyclovir in pharmaceutical solid dosage forms through their poly(vinyl chloride) blister package by solid-state Fourier transform Raman spectroscopy

Fourier transform (FT) Raman spectroscopy based on band intensity or band area measurements was used for the quantitative determination of acyclovir in pharmaceutical solid dosage forms through their poly(vinyl chloride) blister package. Univariate calibration using the bands observed at 1690, 1630, 1574, 1482, 1181, 578, and 508 cm(-1) was found to be sufficient for the analysis. Calibration curves were linear, the correlation coefficients being 0.997-0.9993 and 0.996-0.9991 for band intensity and band area measurements, respectively. Results obtained compare well, as indicated by the t-test, with those obtained by the current United States Pharmacopoeia (USP 24) and National Formulary (NF 19) method. Precision ranged from 0.7-4.5 and 0.4-4.0% RSD (n = 3) for band intensity and band area measurements, respectively. The developed nondestructive FT-Raman method is rapid, simple, and can be used for the on-line, real-time monitoring of acyclovir formulation production lines.     

Drug characterization in low dosage pharmaceutical tablets using Raman microscopic mapping

Raman micro-spectroscopic mapping is utilized to analyze pharmaceutical tablets containing a low concentration (0.5% w/w) of active pharmaceutical ingredient (API). The domain sizes and spatial distributions of the API and the major excipients are obtained. Domain size of the API is found to be dependent upon the particle size distribution of the ingoing API material, making the Raman maps good indicators of the source of API used in tablet manufacturing. Multivariate classification was performed to simultaneously check for the presence of two undesired API polymorphs within tablets. Raman mapping was demonstrated capable of detecting in the tablet matrix as little as 10% form conversion of the low-dosage (0.5% w/w) API, which is equivalent to detection of a 0.05% w/w polymorphic impurity. Overall, the information provided by Raman micro-spectroscopic mapping was found to have potential utility for manufacturing process optimization or predictive stability assessments.     

Application of Fourier transform infrared spectroscopy in cement Alkali quantification

Alkali in cement is responsible for the Alkali–silica-reaction phenomenon that manifests itself in the form of premature cracking in concrete structures such as bridge decks and concrete pavements. X-ray fluorescence spectroscopy (XRF) is commonly used for cement Alkali quantification but a simpler and faster analytical procedure based on Fourier transform infrared spectroscopy (FTIR) has been expanded for this purpose. An analytical absorption band at 750 cm^?1 in the FTIR spectra of cement samples belonging to Alkali solid solution of tricalcium aluminate [C₃A(ss)] is used for Alkali quantification. Regression analysis of a plot correlating FTIR absorption band area ratio (750/923 cm^?1) to equivalent Alkali Na₂O _e (Na₂O _e  = % Na₂O + 0.658 × % K₂O) measured by XRF shows a linear correlation coefficient, R ², of 0.97. High Alkali cement samples show a higher microstructural disorder coefficient, C _d, which is a reactivity criterion introduced by Bachiorrini and co-authors (Proceedings of the seventh international conference on concrete alkali-aggregate reactions? 1986) for ASR-susceptible aggregates. Results of this research indicate applicability of FTIR technique to quantitatively predict cement vulnerability to ASR through the \( A_{{750\,{\text{cm}}^{ - 1} }} \) to \( A_{{923\,{\text{cm}}^{ - 1} }} \) band area ratio and the magnitude of the disorder coefficient (C _d).