Validated spectrofluorimetric method for the determination of netilmicin based on its interaction with o-phthalaldehyde/mercaptoethanol: Evaluation of the method's greenness.

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o-phthalaldehyde/2-mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λemission of 434 nm after λexcitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch-on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30-210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co-formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON.

Sustainable chromatographic quantitation of multi-antihypertensive medications: application on diverse combinations containing hydrochlorothiazide along with LC-MS/MS profiling of potential impurities: greenness and whiteness evaluation.

Cardiovascular disorders are among the leading causes of death worldwide, especially hypertension, a silent killer syndrome requiring multiple drug therapy for appropriate management. Hydrochlorothiazide is an extensively utilized thiazide diuretic that combines with several antihypertensive drugs for effective treatment of hypertension. In this study, sustainable, innovative and accurate high performance liquid chromatographic methods with diode array and tandem mass detectors (HPLC-DAD and LC-MS/MS) were developed, optimized and validated for the concurrent determination of Hydrochlorothiazide (HCT) along with five antihypertensive drugs, namely; Valsartan (VAL), Amlodipine besylate (AML), Atenolol (ATN), Amiloride hydrochloride (AMI), and Candesartan cilextil (CAN) in their diverse pharmaceutical dosage forms and in the presence of Chlorothiazide (CT) and Salamide (DSA) as HCT officially identified impurities. The HPLC-DAD separation was achieved utilizing Inertsil ODS-3 C18 column (250 × 4.6 mm, 5 µm) attached with photodiode array detection at 225.0 nm. Gradient elution was performed utilizing a mixture of solvent A (20.0 mM potassium dihydrogen phosphate, pH 3.0 ± 0.2, adjusted with phosphoric acid) and solvent B (acetonitrile) at ambient temperature. Linearity ranges were 0.1-100.0 µg/mL for HCT, VAL, AML and CAN, 0.05 -100.0 µg/mL for both ATN and AMI and 0.05-8.0 µg/mL for both CT and DSA. Additionally, this work describes the use of liquid chromatography-electrospray-tandem mass spectrometry for the accurate detection and quantification of the impurities; CT and DSA in the negative mode utilizing triple quadrupole mass spectrometry. The linearity ranges for those impurities were 1.0-200.0 ng/mL and 5.0-200.0 ng/mL for CT and DSA, respectively. Developed methods' validation was achieved in accordance with International Conference on Harmonization (ICH) guidelines. Upon applying liquid chromatographic techniques for the drug analysis, a green and sustainable assessment have to be handled due to the consumption of energy and many solvents. Through the use of the HEXAGON, Analytical Greenness (AGREE) and White Analytical Chemistry (WAC) tools, greenness and sustainability have been statistically assessed. The optimized HPLC-DAD and LC-MS/MS methods were fast, accurate, precise, and sensitive, and consequently could be applied for conventional analysis and quality control of the proposed drugs in their miscellaneous dosage forms for the purpose of reducing laboratory wastes, time of the analysis time, effort, and cost.

Erratum to "Spider diagram and sustainability evaluation of UV-methods strategy for quantification of aspirin and sildenafil citrate in the presence of salicylic acid in their bulk and formulation" [Heliyon 9(4) (April 2023) e15260].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15260.].

Spider diagram and sustainability evaluation of UV-methods strategy for quantification of aspirin and sildenafil citrate in the presence of salicylic acid in their bulk and formulation.

The cutting-edge combination of aspirin (ASA) and sildenafil citrate (SIC) has been presented as a suggested dosage form for the treatment of thin endometrium and erectile dysfunction, particularly in patients with cardiovascular diseases. However, ASA is highly sensitive to degradation into its major deterioration product, known as salicylic acid (SA). Consequently, it is eminently essential to evolve approaches for the synchronous quantification of ASA and SIC in the presence of SA. The main objective of this work is to develop three approaches for the synchronous quantification of ASA and SIC in the presence of SA in their commixtures and suggested formulations without any prior separation. Three green UV-methods were employed for the synchronous quantification, namely: Dual Wavelength in Ratio Spectra (DW-RS), Advanced Amplitude Centering (AAC), and Double Divisor of Ratio Difference Derivative (DDRD-D1). In DW-RS and AAC two-wavelength manipulation was used for resolution, while in DDRD-D1 only an appropriate wavelength for the synchronous quantification of the triplex commixture was used. All approaches can be able to resolve the highly interfering spectrum of the three components presented in the triplex commixture. Good linearity was inspected in the range of 20.0-100.0, 5.0-50.0, and 4.0-60.0 µg/mL for the ASA, SIC, and SA, respectively. All developed approaches have been advocated in accordance with ICH guidelines. All results from these approaches are presented and statistically reconciled with the proclaimed HPLC method, with no considerable differences. Furthermore, the approaches' eco-friendliness was predestined by Analytical Greenness (AGREE), and the complex GAPI. Moreover, the sustainability of the used solvent was evaluated by Green Solvents Selecting Tool (GSST); in addition, the greenness of the solvent was evaluated by Greenness Index tool with a spider diagram. The suggested UV-methods may be employed for routine quality control studies of the suggested formulations ASA & SIC since they were considered sustainable, economical, and effective.

New spectral resolution techniques for resolving and determining the components in binary fixed-dose combinations.

Four spectrophotometric approaches were performed to determine a binary combination of Phenazone and Benzocaine in pure powder form and in pharmaceutical formations. This investigation submits the application of four techniques contingent on the presence of the extended area of the spectra of one compound in the binary mixture, these methods include Absorptivity Centering (a-centering), Absorbance Subtraction (AS), Amplitude Modulation (AM) and Concentration Value (CV). The linearity range for the above-mentioned approaches was found to be 3.0-15.0 µg/mL for Benzocaine in a-centering method and 3.0-30.0 µg/mL for Benzocaine and Phenazone in other advanced methods. The four techniques were evaluated as per ICH criteria and were successfully utilized for the determination of Phenazone and Benzocaine existing in pharmaceutical formulations. All results gained by the submitted approaches were statistically compared with a previously published method, and no important differences were detected.

Fingerprint Spectrophotometric Methods for the Determination of Co-Formulated Otic Solution of Ciprofloxacin and Fluocinolone Acetonide in Their Challengeable Ratio.

Six spectrophotometric methods were developed to determine a new single-dose otic solution known as "Otovel®," which consists of two components: the major one is ciprofloxacin (CIP) and the minor is fluocinolone acetonide (FLU). The ratio of (CIP) and (FLU) in Otovel® is 12 : 1, which is considered a challengeable ratio for UV determination. Thus, spectrum addition as a sample enrichment technique was required for the analysis of (FLU) low concentration. All these methods were capable of resolving the spectra for each component in D 0 belonging to the fingerprint resolution technique. The former absorptivity centering (a-centering) method was recently developed in 2018; it was effectively applied for its solution of both binary components in Otovel®, while another method, ratio subtraction (RS), is considered as an original resolution method that could be applied to determine only one component in mixtures. However, the other four methods that are related to their original method (RS) were extended ratio subtraction (EXRS), constant multiplication (CM), unified constant subtraction (UCS), and spectrum subtraction (SS). They were also easily applied for completing the quantification of binary mixture drugs present in Otovel®. The linearity ranges were found to be 3.0-15.0 µg/mL for (CIP) and (FLU), respectively. All results acquired from the proposed methods were successfully estimated according to ICH criteria and were statistically compared with official ones where no differences were noticed.

Spectrophotometric strategies for the analysis of binary combinations with minor component based on isoabsorptive point's leveling effect: An application on ciprofloxacin and fluocinolone acetonide in their recently delivered co-formulation.

Comparative study of the spectrophotometric strategies utilizing the isoabsorptive point present in overlapped absorption spectra of ciprofloxacin and fluocinolone acetonide in their recently delivered co-formulation, was presented. Four spectrophotometric approaches were developed, dependent on the determination of the leveling effect of isoabsorptive point in their zero order absorption spectra or its manipulated form ratio spectra as it retains an isosbestic point. The proposed strategy was based on determination of the total concentrations of the proposed drugs at iso-point, either via zero order or ratio spectra, while one of the recommended methods determined the concentration of the major component, so the concentration of the minor component was obtained by differentiation. The first, second and third methods are utilizing isoabsorptive point at zero order absorption spectrum to quantify total concentration of the cited component, while the major component could be selectively determined using either absorbance at its maxima (IsoPD0-D0max), or area under the peak method (IsoPD0-AUC), or first derivative technique (IsoPD0-D1). The fourth method is ratio manipulated isoabsorptive point in ratio spectrum, namely the amplitude modulation method (AM), using an unified regression equation for the total and major component concentrations, separately. The four methods were applied practically for the analysis of the binary mixtures of ciprofloxacin hydrochloride (CIP) and fluocinolone acetonide (FLU) in a recently otic solution form in challengeable ratio12:1respectively, without the need of any previous stages such as separation, dilution or standard addition. The methods were successfully validated as per ICH guidelines. The outcomes data gained from those submitted techniques were statistically assimilated with official ones. However, no radical differences were noticed.