RESUMEN
Three novel, simple and accurate multivariate spectrophotometric assisted mathematical techniques were developed for determination of paracetamol, caffeine, drotaverine HCl and their related impurities. The used multivariate algorithms are principal component regression (PCR), partial least squares (PLS), and synergy intervals partial least squares (siPLS). Linearity of the suggested methods was found to be (1.00-14.60, 1.40-7.00, 1.40-3.80, 1.00-3.00, 1.50-3.50 and 2.50-4.50 µg/mL) for paracetamol, caffeine, drotaverine HCl, and their related impurities; p-aminophenol, theophylline and homoveratric acid, correspondingly. The presented methods were effectively implemented in the determination of the cited compounds in their laboratory prepared mixtures. Commercially available tablet preparation was also analyzed using the applied methods where no impurities were detected and without interference from tablet additives. Moreover, statistical analysis did not reveal any noticeable differences between the obtained results and those acquired from the reported method in terms of accuracy and precision. The developed multivariate algorithms were validated by means of internal and external validation sets. The obtained results showed the siPLS algorithm's superiority to PCR and PLS according to the values of correlation coefficient values (r) and the lowest root mean square error of prediction (RMSEP). The combination of four subintervals [10, 12, 14, and 17] produced the highest efficiency model. Furthermore, these methods may be an applicable substitute to HPLC ones in quality control laboratories during rush of analyses where several samples have to be analyzed in a short time.
RESUMEN
A sensitive, specific and eco-friendly reversed-phase-HPLC method was developed and validated for the determination of paracetamol, caffeine and drotaverine HCl along with their related impurities. The separation was accomplished using an X-bridge C18 column (5 µm; 250 mm × 4.6 mm inner diameter) and a green mobile phase consisting of methanol and 0.02 M phosphate buffer at pH 5.0 in the gradient elution mode. The detector used was a diode array detector. The proposed method was validated in accordance with the International Conference on Harmonisation guidelines. Linear regressions were found in the range of 1-100, 1-100, 2-60, 1-20, 0.50-30 and 1-15 µg/mL for paracetamol, caffeine, drotaverine HCl, p-aminophenol, theophylline and 3,4-dimethoxyphenylacetic acid, respectively. The suggested method was successfully applied for the determination of the studied drugs in their tablet dosage form without interference from any excipients. No discernible difference was found between the obtained results and official or reported methods, statistically, in terms of both accuracy and precision. Dissolution profiling of the studied tablet was also performed using the suggested procedure. Moreover, the greenness profile was assessed using three different tools, namely, the National Environmental Methods Index, the Analytical Eco-Scale and the Analytical GREEnness Metric Approach. The acquired results assert the agreement of the assay with green chemistry principles.