Different Eco-Friendly Spectrophotometric Approaches Including Direct and Manipulations of Zero and Ratio Spectra for Simultaneous Determination of Novel Nasal Spray Combination Used in Seasonal Allergic Rhinitis.

BACKGROUND: The presentation of rhinitis has drawn increasing attention in recent years due to the possibility of overlap or confusion between allergic rhinitis symptoms and those of COVID-19. Azelastine hydrochloride (AZH) and mometasone furoate (MOF) are two of the most efficient combinations for enhancing the symptoms of seasonal allergic rhinitis. OBJECTIVE: This work concerns applying and validating different accurate and simple spectrophotometric approaches for simultaneous quantification of the binary mixture of AZH and MOF in raw material, laboratory-prepared mixtures, and pharmaceutical preparation. Moreover, assessment of the environmental impact of the applied approaches on the environment was also a key goal of this study. METHODS: AZH was determined using the direct spectrophotometric (D0) method, while four reliable spectrophotometric approaches namely, induced dual wavelength (IDW), ratio subtraction (RS), ratio difference (RD), and ratio derivative (1DD) were used for MOF determination. RESULTS: The methods were validated in line with the International Conference of Harmonization standards. In the AZH range of (5-56 µg/mL) and MOF range of (2-20 µg/mL), the linearity of the proposed approaches was investigated with high accuracy findings. There were no significant differences between the obtained results and those of the reported method when compared statistically. Furthermore, the applied spectrophotometric methods were deemed to be eco-friendly according to Green Analytical Procedure Index (GAPI) and Analytical Greenness Calculator (AGREE) assessment metrics. CONCLUSIONS: The applied spectrophotometric methods are simpler, more eco-friendly, and take a shorter time to precisely estimate many measurements compared to the only reported chromatographic analysis. HIGHLIGHTS: Neither publications of novel spectrophotometric methods nor reported green ones have been available for simultaneous determination of the binary mixture of AZH and MOF, so this work has a great significance and novelty in the area of pharmaceutical analysis.

A Validated Ultra-Performance Liquid Chromatographic Method for the Simultaneous Determination of Nadifloxacin, Mometasone Furoate and Miconazole Nitrate in Their Combined Dosage Form and Spiked Human Plasma Samples.

Nadifloxacin, mometasone furoate and miconazole nitrate are formulated together as a topical antifungal dosage form. In this work, a reversed-phase ultra-performance liquid chromatographic method coupled with a diode array detector (RP-UPLC-DAD) was developed and validated to determine nadifloxacin, mometasone furoate and miconazole nitrate simultaneously in their bulk powder, in pharmaceutical preparation and in spiked human plasma samples. Separation was achieved on an ACQUITY UPLC C18 column of 2.2 µm particle size (2.1 × 100 mm) via isocratic elution using a mobile phase consisting of methanol, acetonitrile and water with ratio (50:20:30; v/v/v) and 0.1 g ammonium acetate, then pH was adjusted to (7.00) using acetic acid, flow rate 0.6 mL/min, temperature 30°C and UV detection at 220 nm. The method is linear in a range from 5 to 400 µg/mL for both nadifloxacin and miconazole nitrate and from 20 to 500 µg/mL for mometasone furoate. The method was validated according to the ICH guidelines then applied successfully to determine the mentioned drugs in their pharmaceutical preparation and spiked human plasma samples. For plasma samples, the results showed that the method can determine nadifloxacin, mometasone furoate and miconazole nitrate in human plasma samples with high accuracy and precision.

Cleaning Validation for Residual Estimation of Mometasone Furoate on Stainless-Steel Surface of Pharmaceutical Manufacturing Equipment Using a UHPLC-UV Method.

Cleaning validation is the documented evidence that shows the effectiveness of cleaning procedures for the removal of product residues and other contaminants. The cleaning procedures must be validated and methods to determine trace amounts of drugs have to be considered with special attention. An ultra-high-performance liquid chromatography-ultraviolet (UHPLC-UV) method for the determination of mometasone furoate residues on stainless-steel surfaces was developed and validated in order to control a cleaning procedure. The chromatography separation was achieved on a Waters Acquity UPLC HSS T3 column (50 × 2.1 mm, 1.8 µm) at 40°C using acetonitrile and water (1:1, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The injection volume was 2 µL, and the detection was performed at 254 nm. The swab and rinse procedures were optimized in order to obtain a recovery higher than 90% of mometasone furoate from stainless-steel surfaces, using ethanol as the extraction solvent. The method was validated in the range of 0.2-2.6 µg/mL and showed appropriate selectivity, limit of detection and quantification, linearity, precision, accuracy, and robustness. This method was found to be simple, fast, and sensitive for determination of mometasone furoate residues and, therefore, can be used for cleaning validation analysis.

Validated Stability-Indicating Methods for Determination of Mometasone Furoate in Presence of its Alkaline Degradation Product.

Two novel stability-indicating TLC densitometric and chemometric methods were developed for the determination of mometasone furoate (MF) in the presence of its alkaline degradation product (MF Deg). The developed TLC densitometric method (Method A) is based on the quantitative densitometric separation of MF from its alkaline degradation product on silica gel 60 F254 and measurement of the bands at 250 nm. The separation was carried out using hexane-chloroform-methanol-acetonitrile (6:6:1:0.3, by volume) as a developing system. A well-resolved and compact bands for (MF) and (MF Deg) at retention factors 0.36 and 0.66, respectively. Good resolution between (MF) and (MF Deg) assured the specificity of the proposed method. The method showed good linearity in the concentration range 0.5-5 µg/band with r2 = 0.9998. The method validation was performed according to ICH guidelines demonstrating to be accurate, precise, robust and sensitive. The LOD and LOQ were found to be 0.21 and 0.63 µg/band for MF, respectively. The developed TLC-densitometric method can be applied for identification and quantitative determination of MF in bulk drug and pharmaceutical dosage forms without any interference from excipients and degradates. Method B is a multivariate chemometric-assisted spectrophotometry, where classical least squares, principal component regression and partial least squares were applied. Statistical analysis of the results has been carried out revealing high accuracy and good precision.

Evaluation of graphical and statistical representation of analytical signals of spectrophotometric methods.

Simultaneous determination of miconazole (MIC), mometasone furaoate (MF), and gentamicin (GEN) in their pharmaceutical combination. Gentamicin determination is based on derivatization with of o-phthalaldehyde reagent (OPA) without any interference of other cited drugs, while the spectra of MIC and MF are resolved using both successive and progressive resolution techniques. The first derivative spectrum of MF is measured using constant multiplication or spectrum subtraction, while its recovered zero order spectrum is obtained using derivative transformation. Beside the application of constant value method. Zero order spectrum of MIC is obtained by derivative transformation after getting its first derivative spectrum by derivative subtraction method. The novel method namely, differential amplitude modulation is used to get the concentration of MF and MIC, while the novel graphical method namely, concentration value is used to get the concentration of MIC, MF, and GEN. Accuracy and precision testing of the developed methods show good results. Specificity of the methods is ensured and is successfully applied for the analysis of pharmaceutical formulation of the three drugs in combination. ICH guidelines are used for validation of the proposed methods. Statistical data are calculated, and the results are satisfactory revealing no significant difference regarding accuracy and precision.