Green Multi-Platform Solution for the Quantification of Levodopa Enantiomeric Excess in Solid-State Mixtures for Pharmacological Formulations.

Regina Presutto,Federico Marini,Alessandra Biancolillo,Stefano Battistoni

doi:10.3390/molecules26164944

Regina Presutto, Federico Marini + Show 2 more

Open Access

https://doi.org/10.3390/molecules26164944

Copy DOI

Abstract

The aim of the present work was to develop a green multi-platform methodology for the quantification of l-DOPA in solid-state mixtures by means of MIR and NIR spectroscopy. In order to achieve this goal, 33 mixtures of racemic and pure l-DOPA were prepared and analyzed. Once spectra were collected, partial least squares (PLS) was exploited to individually model the two different data blocks. Additionally, three different multi-block approaches (mid-level data fusion, sequential and orthogonalized partial least squares, and sequential and orthogonalized covariance selection) were used in order to simultaneously handle data from the different platforms. The outcome of the chemometric analysis highlighted the quantification of the enantiomeric excess of l-DOPA in enantiomeric mixtures in the solid state, which was possible by coupling NIR and PLS, and, to a lesser extent, by using MIR. The multi-platform approach provided a higher accuracy than the individual block analysis, indicating that the association of MIR and NIR spectral data, especially by means of SO-PLS, represents a valid solution for the quantification of the l-DOPA excess in enantiomeric mixtures.

Highlights

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
3,4-dihydroxyphenylalanine, an amino-acid better known as DOPA, is a chiral active pharmaceutical ingredient (API) consisting of two enantiomers, L-DOPA and DDOPA, used to treat medical conditions resulting in dopamine deficiency (e.g., Parkinson’s disease)
In order to achieve this goal, MIR and near infrared (NIR) spectroscopies were used in combination with two different regression models: partial least squares (PLS) and sequential and orthogonalized partial least squares (SO-PLS)

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Racemic DOPA is orally administered in combination with inhibitors of peripheral decarboxylases It is therapeutically not active but is useful for increasing the effectiveness of treatment and decreasing the risk of side effects [1]. The most natural way of assessing the enantiomeric excess in formulations is by means of polarimetric analysis, exploiting the rotatory power of the API [3]. This approach is the one suggested by the European Pharmacopoeia; the application of this technique is not the most suitable solution for small concentrations of the enantiomer of interest

Objectives

Results

Conclusion