Enhancing the Sustainability of Eco-Friendly Potentiometric Ion-Selective Electrodes for Stability-Indicating Measurement of Ethamsylate: Application in Bulk and Pharmaceutical Formulations.

BACKGROUND: Through the use of sustainable and green chemistry concepts, scientists need to decrease waste, conserve energy, and develop safe substitutes for hazardous compounds, all for protecting and benefiting society and the environment. OBJECTIVE: Four novel eco-friendly ion selective electrodes (ISE) were generated to determine Ethamsylate (ETM) in bulk powder and different pharmaceutical formulations. The present electrodes were fabricated to clearly distinguish ETM from a variety of inorganic, organic ions, sugars, some common drug excipients and the degradation product, hydroquinone (HQ) of ETM, and thus used for stability-indicating methods. METHODS: The electrodes fabrication was based on 2-nitrophenyl octyl ether (NPOE) that was employed as a plasticizer in electrodes 1, 2, and 3 within a polymeric matrix of polyvinyl chloride (PVC) except for electrode 4, in which dibutyl sebacate was used as a plasticizer. Electrodes 1 and 2 were fabricated using tetradodecylammonium bromide as an anionic exchanger, adding 4-sulfocalix-8-arene as an ionophore only to electrode 2 and preparing electrode 1 without incorporation of an ionophore. The fabrication of electrodes 3 and 4 was based on ethamsylate-tetraphenylborate (ETM-TPB) as an ion-association complex in a PVC matrix. The environmental sustainability was assessed using the green analytical procedure index (GAPI), and analytical greenness metric for sample preparation (AGREEprep). RESULTS: Electrodes 1 and 2 had linear dynamic ranges of 10-1-10-5 mol/L and 10-1-10-4 mol/L, respectively, with a Nernstian slope of 49.6 and 53.2 mV/decade, respectively. Electrodes 3 and 4 had linear dynamic ranges of 10-1-10-4 mol/L, with a Nernstian slope of 43.9 and 40.2 mV/decade, respectively. CONCLUSION: The electrodes' selectivity coefficients showed good selectivity for ETM. The utility of 4-sulfocalix-8-arene as an ionophore had a significant influence on increasing the membrane sensitivity and selectivity of electrode 2 compared to other electrodes. HIGHLIGHTS: Four novel eco-friendly ISEs were used for determination of ETM in bulk powder and different pharmaceutical formulations. Different experimental parameters were performed to optimize the determination conditions such as solvent mediators, dynamic response time, effect of pH, and temperature. Stability-indicating measurement of ETM in the presence of its degradate HQ and co-formulated drug tranexamic acid. Using new ecological assessment tools to determine whiteness and greenness profiles.

Stability-indicating chemometric methods for the determination of tazarotene.

Two multivariate calibration methods-principal component regression (PCR) and partial least square (PLS)-have been used to determine tazarotene in the presence of its degradation products. Both methods are useful in spectral analysis because of the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry. A great improvement in the precision and predictive abilities of these multivariate calibrations was observed. A calibration set was constructed for the mixture and the best model was used to predict the concentration of the selected drug. The proposed methods were applied successfully in the determination of tazarotene in laboratory-prepared mixtures and in commercial preparations. Tazarotene was analyzed with mean accuracies of 100.006 ± 0.695 and 100.007 ± 0.690 using the PCR and PLS methods, respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed methods were found to be rapid, simple and required no preliminary separation. They can therefore be used for the routine analysis of tazarotene in quality-control laboratories.

Stability-indicating spectrophotometric methods for determination of tazarotene in the presence of its alkaline degradation product by derivative spectrophotometric techniques.

The stability of tazarotene (TZ) was investigated and two stability-indicating methods-namely, first derivative and a derivative ratio spectrophotometric method-were used to determine tazarotene in the presence of its alkaline degradation product (HD) using methanol as a solvent. A linear relationship was obtained in the range 1-10 µg ml⁻¹ for both methods. By applying the proposed methods, it was possible to determine tazarotene in its pure powdered from with accuracy 99.35 ± 1.410 (n = 10) for the first derivative method and 99.45 ± 1.053 (n = 10) for the derivative ratio method. First derivative and derivative ratio methods were used for the analysis of laboratory-prepared mixtures containing different ratios of tazarotene and its degradation product and they were valid in the presence of up to 70% and 80% degradation product, respectively. The proposed methods were validated and found to be suitable as stability-indicating assay methods for tazarotene in pharmaceutical formulations.

A validated HPLC method for separation and determination of promethazine enantiomers in pharmaceutical formulations.

A simple, rapid, and validated method for separation and determination of promethazine enantiomers was developed. Promethazine was separated and quantitated on a Vancomycin Chirobiotic V column (250 x 4.6 mm), using a mixture of methanol, acetic acid, and triethylamine (100:0.1:0.1%, by volume) as a mobile phase at 20 degrees C and at a flow rate of 1 mL/min. The UV-detector was set to 254 nm. Acetyl salicylic acid (Aspirin) was used as an internal standard. The applied HPLC method allowed separation and quantification of promethazine enantiomers with good linearity (r > .999) in the studied range. The relative standard deviations (RSD) were 0.29 and 0.36 for the promethazine enantiomers with accuracy of 100.06 and 100.08. The limit of detection and limit of quantification of promethazine enantiomers were found to be 0.04 and 0.07 microg/mL, respectively. The method was validated through the parameters of linearity, accuracy, precision, and robustness. The HPLC method was applied for the quantitative determination of promethazine in pharmaceutical formulations.