Development of eco-friendly spectrophotometric methods for analysis of metformin hydrochloride and linagliptin in presence of metformin toxic impurity in their pure and dosage forms: Validation, practicality and greenness studies.

Metformin is considered as type 2 diabetes first line treatment according to American Diabetes Association and European Association. But, in some cases, di- or tri - therapy should be prescribed for glycemic management, prevention of the maximum dose side effects and induced effectiveness. Co-administration of Linagliptin with metformin has many benefits on diabetic patients such as decrease the possibility of hypoglycemia. For the first time, novel and reliable techniques were developed and verified for the concurrent quantification of metformin hydrochloride and linagliptin, while accounting for the existence of metformin toxic impurity 1-cyanoguanidine in their pure and dosage forms. Method (A) utilizes the zero-order spectrophotometric approach to quantitatively determine the concentration of linagliptin. The measurements are performed at a wavelength of 295 nm. The double divisor derivative ratio spectrophotometric method is used in Method (B) to measure the amounts of metformin and cyanoguanidine at 252 nm and 219 nm wavelengths, respectively. The spectrophotometric method (C) for determining metformin and cyanoguanidine at 252 nm and 223 nm, respectively, is based on the single divisor derivative ratio-zero crossing technique. The obtained findings were subjected to statistical comparison with the reported method, revealing no statistically significant differences. The Green Analytical Procedure Index (GAPI) and Analytical GREEnness Metric approach (AGREE) determined that these approaches had a high degree of environmental friendliness. Additionally, the proposed strategy was deemed to be practical according to the Blue Applicability Grade Index (BAGI) assessment tool.

Development and validation of an eco-friendly HPLC-UV method for determination of atorvastatin and vitamin D3 in pure form and pharmaceutical formulation.

Statin-associated muscle symptoms are considered as obvious adverse effects of prolonged statin therapy such as myopathy, myalgia, and rhabdomyolysis. These side effects are associated with vitamin D3 deficiency and can be adjusted by amendment of serum vitamin D3 level. Green chemistry aims to decrease the harmful effects of analytical procedures. Here we have developed a green and eco-friendly HPLC method for the determination of atorvastatin calcium and vitamin D3. The two drugs were separated in less than 10 min on Symmetry column C18 (100 × 4.6 mm, 3.5 µm) using a mixture consisting of 0.1% ortho-phosphoric acid (OPA) (pH = 2.16) and ethanol as the mobile phase in gradient manner. We have used Green Analytical Procedure Index (GAPI) tools and the Analytical GREEnness Metric Approach (AGREE) for assessment of the greenness of our proposed method. The method proved linearity over concentration ranges of (5-40) and (1-8) µg/ml with low limit of detection of 0.475 and 0.041 µg/ml for atorvastatin calcium and vitamin D3 respectively. The method was successfully validated in accordance with ICH instructions and utilized for determination of the drugs of interest either in pure form or in their pharmaceuticals.

Spectral analysis of severely overlapping spectra based on newly developed mathematical filtration techniques and ratio spectra manipulations: An application to the concurrent determination of dapoxetine and sildenafil in combined dosage form.

BACKGROUND: Dapoxetine hydrochloride (DAP) and sildenafil citrate (SIL) have proven clinically effective in the treatment of comorbid conditions like erectile dysfunction and premature ejaculation. The analysis of DAP and SIL combinations represents a challenge because of the severe overlap of these compounds' spectra. Six newly developed methods were proven effective for resolving such a challenging overlap. They also exhibited the advantage of simplicity as they depend on the zero-order spectrum and only require simple mathematical handling. OBJECTIVE: We suggested six simple, precise, and sensitive spectrophotometric methods based on mathematical filtration techniques and ratio spectra manipulations to resolve the spectra of DAP and SIL in their bulk and combined pharmaceutical dosage form and estimate the relevant individual concentrations. METHODS: The first three methods were based on the zero-order range and involved modest mathematical manipulations. They are the induced dual-wavelength, Fourier self-deconvolution, and absorptivity factor spectrophotometric methods. Three other methods that are based on ratio spectra manipulation were developed: ratio difference, mean centering of the ratio spectra, and derivative ratio spectrum. RESULTS: We determined the performance of the suggested methods for estimating DAP and SIL in their laboratory mixtures and their combined pharmaceutical dosage form. The linear ranges for DAP and SIL were 1-40 µg/ml and 2-60 µg/ml, respectively. The detection limits were in the 0.18-1.10 µg/ml range for DAP and in the 0.68-1.11 µg/ml range for SIL. The developed methods were validated as per the ICH guidelines for linearity, detection limit, quantitation limit, selectivity, precision, and accuracy. Normal probability, interval, and Tukey's simultaneous significant difference plots were utilized to confirm and better visualize the analysis of variance test results. Statistically, no significant difference was observed to exist between results obtained from the hereby developed and the previously reported methods.

Smart UV spectrophotometric methods based on simple mathematical filtration and classical methods for the simultaneous determination of tamsulosin and solifenacin: A comparative study of efficacy and spectral resolution.

Treatment protocols combining tamsulosin and solifenacin proved better management of the complicated urinary tract symptoms. The pharmaceutical preparations of tamsulosin and solifenacin suffered from the high difference in their ratio, 0.4 mg tamsulosin and 6 mg solifenacin, and strong spectral overlap. Here, we developed four simple, accurate and selective spectrophotometric methods based on simple mathematical manipulations. These methods require the simplest mathematical filtration using short steps performed using built-in functions of the spectrophotometer operating software utilizing zero-order or derivative spectra. These methods are namely absorption correction method (ACM), induced dual-wavelength (IDW), absorptivity factor method (AFM) and first derivative method (D1). The linear ranges were 15-70 µg/ml and 100-1200 µg/ml for TAM and SFN, respectively. The limits of quantitation were in the range of 3.8-4.05 µg/ml and 23.34-59.05 µg/ml, while the limits of detection were in the range of 1.25-1.34 µg/ml and 7.7-24.6 µg/ml for TAM and SFN, respectively. All validation parameters investigated as per ICH guidelines. A statistical comparison executed for the proposed methods with each other and with the reported methods showed no significant difference between the proposed and the reported methods.

An enhanced first derivative synchronous spectrofluorimetric method for determination of the newly co-formulated drugs, amlodipine and celecoxib in pharmaceutical preparation and human plasma.

BACKGROUND: A new combination of amlodipine and celecoxib has been recently introduced in order to relieve the symptoms of osteoarthritis and help treat hypertension that commonly associated with osteoarthritis. OBJECTIVE: The current study is the first to develop and optimize a sensitive, simple and accurate first derivative synchronous spectrofluorimetric method for the simultaneous determination of amlodipine and celecoxib in bulk powder, pharmaceutical preparation and spiked human plasma. METHOD: The method implies the use of synchronous methodology using Δλ = 100 nm and measuring the fluorescence amplitudes of the first derivative each at the zero-crossing point of the other. For amlodipine and celecoxib, the emission wavelengths were at 455 nm and 368 nm, after excitation at 367 nm and 264 nm, respectively. RESULTS: The method was found to be linear over a wide concentration ranges of (5-600 ng/ml), (100-2000 ng/ml) with lower limits of detection of (1.16 ng/ml) and (17.16 ng/ml) for amlodipine and celecoxib, respectively. Enhancement of the fluorescence intensity was achieved by complex formation between the studied drugs and the surfactant sodium dodecyl sulfate and optimizing other experimental conditions. The method was further extended for application for determination of the studied drugs in spiked human plasma with excellent % recoveries of (95.20 ± 6.095) and (98.67 ± 6.394) for amlodipine and celecoxib, respectively. Validation of the method was successfully implemented according to recommendations delivered by guidelines of the International Conference on Harmonization.

Simultaneous determination of Nebivolol hydrochloride and Valsartan in their binary mixture using different validated spectrophotometric methods.

Five simple, sensitive, accurate and precise spectrophotometric methods were developed for the simultaneous determination of Nebivolol hydrochloride (NEB) and Valsartan (VAL) in their binary mixtures and in pharmaceutical dosage form. The methods included Ratio Difference, First Derivative ratio, Mean Centering of ratio spectra, Bivariate and H-Point Standard additions method. The calibration curves were linear over the concentration range of 10-70 µg/ml and 20-60 µg/ml for NEB and VAL, respectively for Ratio Difference and First Derivative ratio method and over the concentration range of 10-70 µg/ml and 10-60 µg/ml for NEB and VAL, respectively for Mean Centering of ratio spectra, Bivariate and H-Point Standard additions method. These methods were examined by analyzing synthetic mixtures of the studied drugs and they were utilized to determine the studied drugs in their commercial pharmaceutical preparation. All methods were validated as per ICH guidelines and accuracy, robustness, repeatability and precision were found to be within the acceptable limits. The results of the proposed methods were compared to the results of reported methods with no significant difference between them.

Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations.

Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at lambda(max) 470nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70microgmL(-1) for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

Utility of NBD-Cl for the spectrophotometric determination of some skeletal muscle relaxant and antihistaminic drugs.

A simple, accurate, precise and sensitive colorimetric method for the determination of some skeletal muscle relaxant drugs, namely orphenadrine citrate (I), baclofen (II), antihistaminic drugs as acrivastine (III) and fexofenadine hydrochloride (IV) is described. This method is based on the formation of charge transfer complex with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in non-aqueous medium. The orange color products were measured at 472, 465, 475 and 469 nm for drugs I, II, III and IV, respectively. The optimization of various experimental conditions was described. Beer's Law was obeyed in the range (2.5-17.5), (5-70), (2.5-25) and (10-50)microg/ml for drugs I, II, III and IV, respectively. The molar absorptivity (epsilon), sandell sensitivity, detection((LOD)) and quantitation limits((LOQ)) are calculated. The procedure was favorably applied for determination of certain pharmaceutical dosage forms containing the studied drugs. The obtained results were compared with the official and reported methods. There were no significant differences between proposed, reported and the official methods.

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride.

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acyclovir and acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drugs with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320nm or the fluorescence intensity of the produced cerous(III) ion at 361-363nm (excitation at 250nm). Beer's law obeyed from 2 to 8, 0.25 to 2.5microgcm-1 acyclovir, 1 to 7 and 0.25 to 2.5microgml-1 acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed method were successfully applied for determination of the selected drugs in their pharmaceutical preparations with good recoveries.

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride.

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drug with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320 nm or the fluorescence intensity of the produced cerous(III) ion at 363 nm (excitation at 250 nm). Beer's law obeyed from 1.0-7.0 microg ml(-1) and 0.25-2.5 microg ml(-1) acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed methods were successfully applied for determination of the selected drug in its pharmaceutical preparation with good recoveries.

Spectrophotometric and spectrofluorimetric methods for analysis of tramadol, acebutolol and dothiepin in pharmaceutical preparations.

Sensitive spectrophotometric and spectrofluorimetric methods are described for the determination of tramadol, acebutolol and dothiepin (dosulepin) hydrochlorides. The two methods are based on the condensation of the cited drugs with the mixed anhydrides of malonic and acetic acids at 60 degrees C for 25-40 min. The coloured condensation products are suitable for the spectrophotometric and spectrofluorimetric determination at 329-333 and 431-434 nm (excitation at 389 nm), respectively. For the spectrophotometric method, Beer's law was obeyed from 0.5 to 2.5 microg ml(-1) for tramadol, dothiepin and 5-25 microg ml(-1) for acebutolol. Using the spectrofluorimetric method linearity ranged from 0.25 to 1.25 microg ml(-1) for tramadol, dothiepin and 1-5 microg ml(-1) for acebutolol. Mean percentage recoveries for the spectrophotometric method were 99.68+/-1.00, 99.95+/-1.11 and 99.72+/-1.01 for tramadol, acebutolol and dothiepin, respectively and for the spectrofluorimetric method, recoveries were 99.5+/-0.844, 100.32+/-0.969 and 99.82+/-1.15 for the three drugs, respectively. The optimum experimental parameters for the reaction has been studied. The validity of the described procedures was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed methods were successfully applied for the determination of the selected drugs in their pharmaceutical preparations with good recoveries. The procedures were accurate, simple and suitable for quality control application.