Determination of linagliptin and empagliflozin by UPLC and HPTLC techniques aided by lean six sigma approach.

Two chromatographic techniques were developed and validated for simultaneous determination of the newly co-formulated antidiabetic combination linagliptin and empagliflozin in their pure form and film-coated tables. The first technique was UPLC; the separation and resolution of both analytes were achieved using a Zorbax eclipse plus C18 column applying an isocratic elution based on phosphate buffer pH 4-acetonitrile (65:35, v/v) as a running mobile phase at flow rate 1.5 ml/min and the effluent was monitored at 220 nm. Augmentation of Lean Six Sigma with UPLC and HPTLC methods had a major impact on the development of robust specifications to ensure that the quality at six sigma level has a high level of statistical confidence and target performance. On the chromatogram, empagliflozin and linagliptin appeared at retention times of 1.417 and 2.453 min, respectively. The second technique was HPTLC; both analytes were fairly well resolved and separated using a developing mobile phase composed of ethyl acetate-chloroform-acetonitrile (55:25:20 by volume). The values of retention factor (RF ) were 0.29 and 0.53 for linagliptin and empagliflozin, respectively. All variables were investigated to adjust the whole conditions.

Simultaneous determination of citalopram and tadalafil by the second derivative synchronous fluorescence method in biological fluids; application of Box-Behnken optimization design.

This is the first study focusing solely on that determination of tadalafil in the presence of citalopram as an antidepressant drug. The determination in biological fluids of a co-administered antidepressant drug and a sexual stimulation drug is a very critical and important step for psychotic and ischaemic heart disease patients, especially in cases of emergency and this requires therapeutic drug monitoring. A sensitive, efficient and rapid assay was selected satisfactorily and applied for simultaneous determination of citalopram and tadalafil either in their pure forms, in tablet dosage forms or in spiked human plasma. There was a large overlap for both drugs, forming the broad band found in conventional fluorescence spectra and their related synchronous fluorescence intensity. Therefore, the development of a highly sensitive second derivative synchronous fluorescence method was demonstrated that removed this overlap. The proposed method depended on measuring the amplitudes of the second derivative of synchronous fluorescence intensity at suitable wavelengths of 301 nm and 367 nm for citalopram and tadalafil at Δλ = 60 nm, respectively. Box-Behnken design as a response surface methodology was used to fit models and create an optimization process encompassing a set of factors and resulting in an optimum response value specifically designed for this method. Under optimum conditions, the linear dynamic ranges for citalopram and tadalafil estimation were 20-900 and 5-400 ng ml-1 with detection limits of 5.40 and 1.43 ng ml-1 , respectively.

Development of an eco-friendly HPLC method for the stability indicating assay of binary mixture of ibuprofen and phenylephrine.

The development and validation of the stability indicating HPLC technique has contributed to the understanding of the stability profile of ibuprofen (IBU) and phenylephrine (PHE). Stability profile was achieved for PHE; the drug was found to be liable to be influenced by stress oxidative conditions; two oxidative degradants (Deg1 & Deg2) were formed and their structures were confirmed using IR and mass spectrometry. The drugs and degradation products were successfully separated using a gradient elution method on YMC-C8 column with 0.1% hexanesulfonic acid and acetonitrile as a mobile phase at pH 6.6. The flow rate was 1.0 mL/min, and a diode array detector operating at 220 nm was used for UV detection. The retention times of degradants Deg1, Deg2, ibuprofen (IBU), and phenylephrine hydrochloride (PHE) were 2.0, 2.2, 3.2 and 7.0 min, respectively. The proposed method was validated with respect to linearity, accuracy, precision, specificity, and robustness using ICH guidelines. The linearities of ibuprofen and phenylephrine hydrochloride were in the range of 10-100 µg/mL and 0.3-10 µg/mL, respectively. The % recoveries of the two drugs were found to be 100.75 ± 1.44%, 99.67% ± 1.67, and the LOD was found to be 2.75/mL and 0.09/mL for IBU, and PHE, respectively. The method was successfully applied to the estimation of ibuprofen and phenylephrine hydrochloride combination in pharmaceutical dosage form. The proposed technique was validated using ICH guidelines and its greenness was assessed according to Analytical Eco Scale metric (AES). Molecular docking was used to assess the two drugs and PHE oxidative degradants interaction with the stationary phase and to confirm the outcomes of the proposed method with regard to the order of elution of the two drugs and PHE degradation products. Eco-friendly and environmental safety were assessed through the application of one of the most applicable greenness assessment tool; Analytical Eco Scale metric (AES).

Three developed spectrophotometric methods for determination of a mixture of ofloxacin and ornidazole; application of greenness assessment tools.

This work is dedicated to the greenness estimation of three proposed spectrophotometric techniques [e.g., ratio difference (RD), mean centering of ratio spectra (MCR) and continuous wavelet transform of ratio spectra (CWT)] for the determination of a binary combination named Ofloxacin (OFL) and Ornidazole (ORN). Applying the green analytical chemistry methods to assess the proposed methods has widely attained the analytical community care. The greenness assessment was performed via three evaluation approaches; the "Analytical Eco-Scale", the "National Environmental Method Index" (NEMI) and "Green Analytical Procedure Index" (GAPI). Following the examination of the zero spectrum of OFL and ORN, it is observed that OFL and ORN spectra are overlapped, so they can be detected by the methods mentioned previously. The ratio difference method was carried out at wavelengths of 294.6 nm and 265.6 nm for OFL, 292 nm and 315 nm for ORN. The linear range was (2-15 µg/mL) for OFL and (3-30 µg/mL) for ORN. The MCR method based on the use of mean centered ratio spectra in dual steps and calculating the second ratio spectra mean centered values at 294.6 nm for OFL and 315 nm for ORN. The continuous wavelet transformation which carried out using MATLAB at wavelengths of 265 nm for OFL and 306 for ORN. These techniques were intended for the binary mixture analysis in bulk powder and pharmaceutical formulations with high recoveries. The developed methods were validated according to ICH guidelines. All techniques were statistically compared to either an official method for OFL or a reported method for ORN and the results indicate that there were not any significant differences.

Novel Deconvoluted Synchronous Spectrofluorimetric Method For Simultaneous Determination Of Bisoprolol and Atorvastatin As Single or Co-administrated Drugs in Bulk and Plasma; Green Assessment.

Atorvastatin and bisoprolol are two medications often prescribed together for the management of cardiovascular disease and to reduce mortality. Through a simple and direct technique based on deconvolution and synchronous of the spectrofluorometric spectra, the innovative method enables simultaneous quantification of bisoprolol and atorvastatin as single or co-formulated dosage forms in bulk and plasma. The method depends on measuring the amplitudes of bisoprolol and atorvastatin at 298 nm and 363 nm directly after deconvolution where the other drug doesn't show interference. The linearity of the method was 0.02-0.5 µg/mL and 0.3-25 µg/mL for bisoprolol and atorvastatin, respectively. LOD and LOQ were 0.004, 0.085 µg/mL and 0.013, 0.259 µg/mL for bisoprolol and atorvastatin respectively. Furthermore, green assessment of the method using Eco-Scale and GAPI scale. The method was precise, economical, simple, smart, time-saving and eco-friendly, which allowed its application in quality control unit and in lab assessment.

Potentiometric determination of mebeverine hydrochloride antispasmodic drug based on molecular docking with different ionophores host-guest inclusion as a theoretical study.

The scientific community has continued to pay particular attention to potentiometric sensors based on ion-selective membrane sensors as an energy-efficient, easy-to-use method suitable for microfabrication. To this end, potentiometric ion-selective sensors were used as an alternative green analytical instrument. Three distinct sensors relying on various ionophores were built and assessed. A cationic exchanger, tetra phenyl borate, was used in the polyvinyl chloride polymeric plasticized matrix using di octyl phthalate, where α, ß, and γ cyclodextrins were utilized as ionophores. A comparative potentiometric analysis was carried out using three ion-selective sensor designs: α, ß, and γ cyclodextrins sensors. ß-Cyclodextrin significantly reduced the detection limit and improved the discriminative performance of mebeverine hydrochloride (MBV) in the pharmaceutical dosage form over α- and γ-cyclodextrins in the presence of other interfering chemicals. Additionally, a significant connection was made between the practical perspective and a theoretical investigation based on computational research. Nernstian potentiometric results for the optimum sensor were obtained for MBV in the range of concentrations 1.0 × 10-2 to 1.0 × 10-6 M, its slope was -58.70 ± 0.12 mV per decade with lower detection limits 4.50 × 10-7 M. This computational molecular docking investigation clarified that the binding sites and modes were in good agreement with the experiment results. This investigation was applied to expect the interaction between MBV and the proposed sensors to ensure which ionophores were the best for MBV.

A screen printed methodology optimized by molecular dynamics simulation and Lean Six Sigma for the determination of xylometazoline in the presence of benzalkonium chloride in nasal drops.

A new chemically disposable screen-printed modified electrode with yttrium doped manganese oxide (Mn2O3/Y2O3) nanocomposite at screen printed electrode was mainly constructed to quantify xylometazoline hydrochloride (XMZ). The crystallographic parameters were estimated from the XRD spectrum, suggesting that Mn2O3 of cubic phase with average grain size ∼ 77 nm. The SEM images revealed that Y3+ dopants had improved the surface topology. The findings indicate that morphological features play a vital role in improving the electronic properties of the fabricated electrode. Augmentation of Six Sigma (SS) with molecular dynamics simulation (MD) as a theoretical study was widely adopted to improve the current process as a quality management methodology by measuring the process capability to determine if the process meets the desired specification limits. Process capability is determined through measuring the variability in the process output and comparing these variations with the desired specifications. Also, it assures a robust method specification at a high level of targeted performance and statistical confidence. A greenness assessment procedure utilizing the eco-scale algorism was conducted to prove the greenness of the proposed methodology. Additionally, the proposed sensor presented a high sensitivity over the concentration range (1x10-6-1x10-2 mol L-1) of a detection limit 3.93 × 10-7 mol L-1 with the Nernstian cationic slope of 58.18 ± 0.76 mV decade-1 at 25 ± 1 °C.

Synthesis of Prussian Blue Analogue and Its Catalytic Activity toward Reduction of Environmentally Toxic Nitroaromatic Pollutants.

Nitroanilines are environmentally toxic pollutants which are released into aquatic systems due to uncontrolled industrialization. Therefore, it is crucial to convert these hazardous nitroanilines into a harmless or beneficial counterpart. In this context, we present the chemical reduction of 4-nitroaniline (4-NA) by NaBH4 utilizing Prussian blue analogue (PBA) as nanocatalyst. PBAs can serve as inexpensive, eco-friendly, and easily fabricated nanocatalysts. PBA cobalt tetracyanonickelate hexacyanochromate (CoTCNi/HCCr) was stoichiometrically prepared by a facile chemical coprecipitation. Chemical, phase, composition, and molecular interactions were investigated by XRD, EDX, XPS, and Raman spectroscopy. Additionally, SEM and TEM micrographs were utilized to visualize the microstructure of the nanomaterial. The findings revealed the synthesized PBA of the cubic phase and their particles in nanosheets. The band gap was estimated from the optical absorption within the UV-vis region to be 3.70 and 4.05 eV. The catalytic performance of PBA for the reduction of 4-NA was monitored by UV-vis spectroscopy. The total reduction time of 4-NA by PBA was achieved within 270 s, and the computed rate constant (k) was 0.0103 s-1. The synthesized PBA nanoparticles have the potential to be used as efficient nanocatalysts for the reduction of different hazardous nitroaromatics.

Innovative electrochemical electrode modified with Al2O3 nanoparticle decorated MWCNTs for ultra-trace determination of tamsulosin and solifenacin in human plasma and urine samples and their pharmaceutical dosage form.

A simple, cheap, sensitive, and time-saving square wave voltammetric (SWV) procedure using a carbon paste electrode modified with aluminum oxide nanoparticle decorated multi-walled carbon nanoparticles (Al2O3-NPs/MWCNTs/CPE) is presented for the ultra-sensitive determination of tamsulosin (TAM) and solifenacin (SOL), one of the most prescribed pharmaceutical combinations in urology. Characterization of the developed electrode was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD) patterns, energy dispersive X-ray analysis (EDX), transmission electron microscopy (TEM) and FT-IR spectrophotometry. The voltammetric behavior of TAM/SOL was evaluated using Al2O3-NPs in different content and electrode compositions. The use of Al2O3 functionalized MWCNTs as a CPE modifier increased the process of electron transfer as well as improved the electrode active surface area therefore, ultra-sensitive results were acquired with a linear range of 10-100 and 12-125 ng ml-1 for TAM and SOL respectively, and a limit of the detection value of 2.69 and 3.25 ng ml-1 for TAM and SOL, respectively. Interestingly, the proposed method succeeded in quantifying TAM and SOL with acceptable percentage recoveries in dosage forms having diverged concentration ranges and in the biological fluids with very low peak plasma concentration (C max). Furthermore, the proposed method was validated, according to the ICH criteria, and shown to be accurate and reproducible.

Computational design for eco-friendly visible spectrophotometric platform used for the assay of the antiviral agent in pharmaceutical dosage form.

Nowadays, the analytical community is focusing on developing new analytical methods that incorporate principles of green analytical chemistry to reduce adverse impacts on the environment and humans. In this study, we focused specifically on establishing a correlated connection between theoretical and experimental applications via developing green, and eco-friendly visible spectrophotometric methods. These methods were relied on charge-transfer complexation (CTC) between ledipasvir and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), or chloranilic acid (CA) for sensitive colorimetric analysis of ledipasvir in the presence of sofosbuvir (Sofolanork plus®). The results were evaluated as modern computational chemistry using molecular modeling technology. At ambient temperature, the reactions for DDQ and CA took 15 and 10 min, respectively, to produce a purple red-colored solution with DDQ absorbing maximally at 588 nm and a purple-colored solution with CA absorbing maximally at 522 nm. Linearity was achieved for ledipasvir utilizing DDQ and CA in the concentration ranges of 8-80 µg.mL-1 and 40-400 µg.mL-1, respectively. The precision and accuracy of the methods mentioned were determined. Finally, the results were statistically compared to a previously published spectrophotometric technique, and no significant differences were found.

Electrochemical determination of dinitolmide in poultry product samples using a highly sensitive Mn2O3/MCNTs-NPs carbon paste electrode aided by greenness assessment tools.

In this paper, chemically modified carbon paste Mn2O3/MCNTs-NPs electrode for estimation of dinitolmide (DOM) utilizing square wave voltammetry method (SWV) was developed. The study investigated the electrochemical behavior of DOM, and the morphology of the modified electrode was evaluated by Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). The voltammetric behavior of DOM at modified electrode was recorded at a scan rate of 100 mVs-1 against Ag/AgCl reference electrode in phosphate buffer pH 4.0 within linearity range 2-12 µM, LOQ, and LOD of 1.8 and 0.594 µM, respectively, with average % recovery of (100.89 ± 0.795). GAPI and Analytical Eco-Scale tools were applied for greenness assessment. Specificity and interference study was valid for the proposed method; allowing DOM to be determined in its acidic degradation and its major interference drug. The proposed method was successfully employed to quantify DOM in bulk powder, egg, and frozen cuts-up chicken muscle samples.

Construction and application of highly sensitive spinel nanocrystalline zinc chromite decorated multiwalled carbon nanotube modified carbon paste electrode (ZnCr2O4@MWCNTs/CPE) for electrochemical determination of alogliptin benzoate in bulk and its dosage form: green chemistry assessment.

A new sensor for alogliptin benzoate (ALG) estimation based on a simple and sensitive method was evolved on multiwalled-carbon-nanotube modified nanocrystalline zinc chromite carbon paste electrodes (ZnCr2O4@MWCNTs/CPEs). ALG electrochemical behavior was evaluated using a cyclic voltammetry (CV), square wave voltammetry (SWV) and chronoamperometry (CA). The new electrode materials were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray analysis (EDX) for elemental analysis and mapping, and X-ray diffraction (XRD) and the X-ray photoelectron spectroscopy (XPS) measurements. All these measurements exhibiting enhanced activity and high conductivity compared to the bare electrode without modification. The calibration curves obtained for ALG were in the ranges of 0.1-20 µmol L-1 with a quantification and detection limits of 0.09 and 0.03 µmol L-1, respectively. The prepared sensor showed a good sensitivity and selectivity with less over potential for ALG determination. Finally, the presented method was successfully applied as a simple, precise and selective electrochemical electrode for the estimation of ALG in its pharmaceutical dosage form.

The fabrication of an innovative extremely sensitive nano green carbon paste electrode amended with the nanocomposite CuO/Y for electrochemical quantification of amprolium in sheep meat and liver samples.

In this work, carbon paste electrode (CPE) and modified CPE with copper oxide or copper yttrium oxide were prepared for determining amprolium hydrochloride (AMP) by differential pulse voltammetry. AMP has an antiprotozoal activity for treating coccidiosis in poultry; their retaining- in sheep meat and livers- induces adversative effects for the customer. XRD pattern was employed to define the fabricated nanostructured materials; the elemental composition of the nanocomposite was examined using EDX spectra. Over a pH ranging from 2 to 8, the oxidation process of AMP was studied using phosphate buffer. The scan rates were studied over a wide range (20 to 140 mV s-1) using cyclic voltammetry. The developed sensor shows a wide linear range (1.0 × 10-8-1.0 × 10-3 M) with a detection limit of 2.32 × 10-9 M. This method can quantify AMP in pharmaceutical form, sheep meat, and liver samples.

Second derivative synchronous fluorescence determination of avanafil in the presence of its acid-induced degradation product aided by powerful Lean Six Sigma tools augmented with D-optimal design.

In this work, the quantitative determination of an erectile dysfunctional drug avanafil in the presence of its acid-induced degradation product was achieved via the application of a pre-optimized novel spectrofluorimetric method. The fluorescence emission wavelength was recorded at 370 and 407 nm, after being excited at 268 and 271 nm for avanafil and its acid-induced degradation product, respectively. Direct determination of avanafil based on its native fluorescence is restricted because the emission spectra of both components are heavily overlapped. Therefore, to overcome this constraint, a novel second derivative synchronous fluorescence method was evolved to eliminate this overlapping. The ideal determination wavelength was found to be 377 nm. Augmentation of lean six sigma (LSS) with response surface methodology (RSM) play a significant role in the development of robust specifications to ensure quality at the six sigma level with a high level of statistical confidence and targeted performance. All of the experimental conditions were optimized using D-optimal design as a RSM to select the optimal parameters. In addition, this work includes a graphical representation of the relationships between various variables that can greatly affect the results and the intensity of the synchronous fluorescence.

Fabrication of an (α-Mn2O3:Co)-decorated CNT highly sensitive screen printed electrode for the optimization and electrochemical determination of cyclobenzaprine hydrochloride using response surface methodology.

A new chemically optimized screen-printed electrode modified with a cobalt-doped α-Mn2O3 nanostructure on carbon nanotube paste (α-Mn2O3:Co@CNTs) has been constructed for the recognition of cyclobenzaprine hydrochloride. The prepared paste is based on the incorporation of oxide ion conductors, such as the α-Mn2O3 nanostructure with cobalt and ion pairs (tetraphenyl borate coupled with the drug), as electroactive species in the screen-printed electrode to increase the sensor surface area and decrease electrical resistance. The central composite design is a useful methodology for the estimation and modeling of the exact optimum parameters specifically designed for this process. This is a good way to graphically clarify the relationship between various experimental variables and the slope response. The proposed sensor, α-Mn2O3:Co@CNTs, possesses very good sensitivity and the ability to recognize the drug over the concentration range of 1 × 10-6 to 1 × 10-2 mol L-1 at 25 ± °C with a detection limit of 2.84 × 10-7 mol L-1. It exhibits a reproducible potential and stable linear response for six months at a Nernstian slope of 58.96 ± 0.76 mV per decade. The proposed electrode approach has been successfully applied in the direct determination of the drug in its pure and dosage forms.

D-optimal design as a useful tool response surface methodology for the optimization of signals from synchronous fluorescence prior to simultaneous determination of avanafil and tadalafil.

A rapid, smart and sensitive first derivative spectrofluorimetric method has been carried out for the simultaneous estimation of avanafil and tadalafil either in their pure form, tablet dosage form or spiked human plasma. The measurements of normal emission spectra or synchronous fluorescence intensity of both drugs show severe overlap which hindered their determination using normal fluorescence or synchronous intensity. Therefore, a highly sensitive first derivative synchronous fluorescence procedure was used to resolve this overlap. The method is based upon measurement of the amplitude of the first derivative of synchronous fluorescence intensity of both drugs at Δλ = 70 nm and at suitable wavelength of 396 nm and 364 nm for avanafil and tadalafil, respectively. Under the optimum conditions, the linear determination ranges are 50-1800 and 5-400 ng mL-1 with a detection limit of 12.93 and 1.46 ng mL-1 for avanafil and tadalafil, respectively. A response surface methodology was used for optimization using D-optimal design which can be used for determination of the exact optimum parameters specifically designed for this method. In addition; it is a good way to graphically clarify the relationship between various experimental variables and the synchronous fluorescence intensity.

Disposable gold nanoparticle functionalized and bare screen-printed electrodes for potentiometric determination of trazodone hydrochloride in pure form and pharmaceutical preparations.

In the present study, screen-printed electrodes unmodified and chemically modified with gold nanoparticles were used as sensitive electrochemical sensors for the determination of trazodone hydrochloride. The sensors were based on the use of a tetraphenylborate ion association complex as an electroactive material in screen-printed electrodes with dioctyl phthalate (DOP) as a solvent mediator modified with gold nanoparticles which improve the electrode conductivity and enhance the surface area. The sensors displayed a stable response for 5, 6 and 7 months with a reproducible potential and linear response over the concentration range 1 × 10-5-1 × 10-2 mol L-1 at 25 ± 1 °C with Nernstian slopes of 57.50 ± 0.66, 58.30 ± 0.45 and 59.05 ± 0.58 mV per decade and detection limits of 7.9 × 10-6, 7.6 × 10-6 and 6.8 × 10-6 mol L-1 for sensor 1, 2 and 3 respectively. The analytical performance of the screen printed electrodes in terms of selectivity coefficients for trazodone hydrochloride relative to the number of potentially interfering substances was investigated. The proposed method has been applied successfully for the analysis of the drug in its pure and dosage forms and there is no interference from any common pharmaceutical additives.