A useful quantitative model for determination of enantiomeric composition of racemate praziquantel by ultraviolet spectroscopy combined with partial least squares and its application to praziquantel tablets

Man Zhao,Haina Wang,Lingyun Hu,Yifang Lu,Lei Nie,Na Sun,Ran Meng

doi:10.1142/s1793545818500116

Abstract

A simple and novel method has been proposed to determine the enantiomeric composition of racemate praziquantel (PZQ) by using the analysis of ultraviolet (UV) spectroscopy combined with partial least squares (PLS). This method does not rely on the use of expensive carbohydrates such as cyclodextrins, but on the use of inexpensive sucrose, which is equally effective as carbohydrate. PZQ has two enantiomers. Through measuring the slight difference in the UV spectral absorption of PZQ due to different interactions between its two enantiomers and sucrose, the enantiomeric composition was determined by a quantitative model based on PLS analysis. The model showed that the correlation coefficients of calibration set and validation set were 0.9971 and 0.9972, respectively. The root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) were 0.0167 and 0.0129, respectively. Then, the independent data of PZQ tablets were also used to test how well the quantitative model of PLS predicted the enantiomeric composition. The ratio of S-PZQ in tablet was 0.492, determined by high-performance liquid chromatography as the reference value. Six solutions of the tablet samples were prepared, and the ratios of S-PZQ in tablet samples in the validation set were predicted by the PLS model. Their relative errors with the reference value were not more than 4%. Therefore, the established model could be accurate and employed to predict the enantiomeric compositions of PZQ tablets.

Highlights

Nowadays, more than one half of the drugs contain chiral centers, marketed as racemates but more and more as single enantiomer
There is a maximum of absorbance in the region from 220 nm to 230 nm even more than 2.8 which is the absorption of solvent, whereas the region from 260 nm to 270 nm has the authentic absorption peak whose value is about 0.5 corresponding to the characteristic absorption of PZQ
Small spectral variations in the UV spectra of PZQ solutions mixed with sucrose were observed when the enantiomeric composition varies by keeping the total concentration of PZQ constant at the same time

Summary

Introduction

More than one half of the drugs contain chiral centers, marketed as racemates but more and more as single enantiomer . Two opposite enantiomers may exert di®erent pharmacological properties, toxicities and side e®ects because of the stereoselective interaction with macromolecules in a biological system.[1] For chiral drug, the structure–activity relationship is critically dependent on the degree of enantiopurity. During the production of a pharmaceutical product, the eudismic ratio, the potency ratio between the more active enantiomer (the eutomer) and the less active one (the distomer), should be taken into account.[2] The Food and Drug Administration (FDA) requires, besides evaluating the e®ect of individual enantiomer, the determination of the purity of all chiral molecules produced, both at the industrial stage and in thenal product.[3] The determination of enantiomeric composition of pharmaceutical chiral product is of capital importance .[4]

Methods

Results

Conclusion