Quantitative Analysis of Entacapone Isomers Using Surface-Enhanced Raman Spectroscopy and Partial Least Squares Regression

Abstract

Surface-enhanced Raman spectroscopy (SERS) and partial least squares (PLS) regression have been applied for the quantification of entacapone isomers E and Z in solution. Nine mixtures of isomers Z and E in ethanol ranging from 0% to 100% w/w were analyzed, for a total entacapone concentration of 1 × 10(-3) mol L(-1). Upon deposition onto commercially available Klarite® gold plates, highly intense and reproducible SERS spectra were obtained from the entacapone isomers. Based on the spectral measurements, a two-component PLS model for correlation of predicted and real content of the isomers mixtures was developed. Root-mean-square error of the predicted composition was found to be 8% of isomer Z in the isomers mixture, corresponding to the absolute concentration of 8 × 10(-5) mol L(-1) of isomer Z in solution.

Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS

“…The vibrational band at ca 1545 cm -1 corresponds to asymmetrical N-O stretching mode. Furthermore, a strong band observed at ca 1440 cm -1 (d CH 2 ) further confirmed the formation of entacapone crystals in the acetone/water and toluene/methanol solutions (6,30).…”

“…1), in the relative ratio of 2:1 (6), but only E-isomer is used as API, since it can be easily isolated from the reaction mixture. Full Surface-enhanced Raman spectroscopy (SERS) has been recently used for quantitative analysis of the two isomers in solution (30). It has also been demonstrated that the E-isomer crystallizes in six polymorphic forms, named A' (25), D (26), a, b, g and d (27), the first two being the most common in polar solvents (28).…”

“…2). The vibrational band around 2200 cm -1 was attributed to the C≡N stretching vibration characteristic of entacapone (6,30). Moreover, two bands observed at ca 1600 and 1580 cm -1 in the in-line Raman spectra obtained in the acetone/water 40:60 and toluene/methanol 30:70 solutions (Fig.…”

“…6). A strong combination band characteristic of E-isomer of entacapone (6,30) was observed at ca 1438 cm -1 . Several weak bands occurred at lower frequencies in the spectral region 1400-1100 cm -1 and can be attributed to C-C, C-O and C-N stretching vibrations.…”

An Augmented Classical Least Squares Method for Quantitative Raman Spectral Analysis against Component Information Loss

“…Inverse/implicit methods can offer accurate prediction results in the situation where only the component(s) of interesting is considered. Therefore, they were much more popular in different applications [15–17] recently. …”