Chemometric quality assessment of Paracetamol and Phenylephrine Hydrochloride with Paracetamol impurities; comparative UV-spectrophotometric implementation of four predictive models.

Spectrophotometric data analysis using multivariate approaches has many useful applications. One of these applications is the analysis of active ingredients in presence of impurities. Four chemometric-assisted spectrophotometric methods, namely, principal component regression (PCR), partial least-squares (PLS), artificial neural networks (ANN) and multivariate curve resolution-alternating least squares (MCR-ALS) were proposed and validated. The developed chemometric methods were compared to resolve the severely overlapped spectrum of Paracetamol (PAR) and Phenylephrine HCl (PHE) along with PAR impurities namely, P-Aminophenol (PAP), P-Nitrophenol (PNP), Acetanilide (ACT) and P-Chloroacetanilide (CAC). The four multivariate calibration methods succeeded in simultaneous determination of PAR and PHE with further quantification of PAR impurities. So, the proposed methods could be used with no need of any separation step and successfully applied for pharmaceutical formulation analysis. Furthermore, statistical comparison between the results obtained by the proposed chemometric methods and the official ones showed no significant differences.

Systemic Optimization and Validation of Normal and Reversed-Phase Eco-Friendly Chromatographic Methods for Simultaneous Determination of Paracetamol and Phenylephrine Hydrochloride in the Presence of Paracetamol Impurities.

BACKGROUND: Chromatographic behavior of different substances in normal and reversed phases is an interesting area in the scientific community. OBJECTIVE: The work aimed to optimize and validate chromatographic separation methods for simultaneous determination of paracetamol (PAR) and phenylephrine HCl (PHE) in the presence of PAR impurities, namely p-aminophenol, p-nitrophenol, acetanilide, and p-chloroacetanilide with further quantification of these toxic impurities. METHODS: TLC method based on normal phase separation was carried out on aluminum sheets of silica gel 60 F254 using ethanol:chloroform:ammonia as a developing system, followed by densitometric measurements. While HPLC is based on reversed phase separation using a C18 column against acetonitrile:phosphate buffer pH 5 as a mobile phase. RESULTS: PAR and PHE were determined by the TLC-densitometric method in concentration ranges of 3-25 and 0.1-3 µg/band, respectively, and determined by the HPLC method over concentration ranges of 5-400 and 2-80 µg/mL, respectively. Both methods were optimized and validated. Furthermore, they were successfully applied for pharmaceutical formulations with precision <2%. Moreover, results of a statistical comparison with the official methods confirm the methods' validity claims. CONCLUSION: Two eco-friendly chromatographic methods were developed to determine PAR and PHE in their binary mixtures, pharmaceutical formulations, and in the presence of PAR-related impurities with further quantification of these toxic impurities. HIGHLIGHTS: These simple chromatographic methods are the first methods developed for simultaneous determination of PAR and PHE in the presence of PAR-related impurities.

Capillary zone electrophoresis as a quality assessment tool of paracetamol and phenylephrine hydrochloride in presence of paracetamol impurities.

The combination of paracetamol (PAR) and phenylephrine HCl (PHE) is a common pharmaceutical combination intended to manage symptoms of every day cold. Since paracetamol is susceptible to degradation or some manufacturing-related impurities, its stability should be monitored continuously. The developed method in this study for the determination of PAR and PHE in presence of PAR impurities is considered a quality assessment tool especially when PAR impurities can be quantitatively determined. A capillary zone electrophoresis (CZE) method was optimized and validated for simultaneous determination of PAR and PHE in presence of PAR impurities namely, p-Aminophenol (PAP), p-Nitrophenol (PNP), Acetanilide (ACT) and p-Chloroacetanilide (CAC) with further quantification of these toxic impurities. Factors that affect the separation quality such as pH, buffer and applied voltage were optimized. The separation was carried out using 20 mM phosphate buffer (pH 8). The linearity was reached over concentration ranges of 30-250 µg/mL, 1-40 µg/mL, 2-50 µg/mL, 2-50 µg/mL, 2-50 µg/mL and 2-50 µg/mL for PAR, PHE, PAP, PNP, ACT, and CAC, respectively, with accuracy ranging from 99.06% to 100.62%. After validation, the method was applied for pharmaceutical formulation analysis with RSD <2%. Moreover, statistical comparison with the official methods confirms that the method is a viable alternative for quality assessment of this combination.

Spectral manipulation of ratio data for simultaneous determination of binary mixture of Paracetamol and Phenylephrine Hydrochloride.

Three ratio spectra manipulating spectrophotometric methods have been developed for determination of Paracetamol (PAR) and Phenylephrine HCl (PHE) in bulk powder and in pharmaceutical formulation. Linear correlations were obtained over the concentration range of 1.0-25.0 µg/mL and 5.0-50.0 µg/mL for PAR and PHE, respectively. The first method is the ratio subtraction method (RS) coupled with constant multiplication (CM) in which PHE was determined by ratio subtraction and PAR was determined by constant multiplication. The second method is the ratio difference method (RD) which depends on measuring the difference between the amplitudes of the ratio spectra at two selected wavelengths. The third method is the first derivative of the ratio spectra (1DD), which allows the determination of PAR at 238.8 and 243 nm and PHE at 213.2, 222.2, 271.8 and 286 nm. The proposed methods are simple, accurate and precise (RSD does not exceed 2%). The applicability of the proposed methods was successfully verified by the analysis of PAR and PHE in pharmaceutical formulation without interference of the dosage form additives. Furthermore, the developed methods were validated according to ICH guidelines, so they are considered to be potential competitors for the analysis of the mixture in quality control labs and pharmaceutical factories.