Nesrine T. Lamie

Simultaneous determination of binary mixture of amlodipine besylate and atenolol based on dual wavelengths

Four, accurate, precise, and sensitive spectrophotometric methods are developed for simultaneous determination of a binary mixture of amlodipine besylate (AM) and atenolol (AT). AM is determined at its λmax 360 nm ((0)D), while atenolol can be determined by four different methods. Method (A) is absorption factor (AF). Method (B) is the new ratio difference method (RD) which measures the difference in amplitudes between 210 and 226 nm. Method (C) is novel constant center spectrophotometric method (CC). Method (D) is mean centering of the ratio spectra (MCR) at 284 nm. The methods are tested by analyzing synthetic mixtures of the cited drugs and they are applied to their commercial pharmaceutical preparation. The validity of results is assessed by applying standard addition technique. The results obtained are found to agree statistically with those obtained by official methods, showing no significant difference with respect to accuracy and precision.

Development of normalized spectra manipulating spectrophotometric methods for simultaneous determination of Dimenhydrinate and Cinnarizine binary mixture

Simultaneous determination of Dimenhydrinate (DIM) and Cinnarizine (CIN) binary mixture with simple procedures were applied. Three ratio manipulating spectrophotometric methods were proposed. Normalized spectrum was utilized as a divisor for simultaneous determination of both drugs with minimum manipulation steps. The proposed methods were simultaneous constant center (SCC), simultaneous derivative ratio spectrophotometry (S(1)DD) and ratio H-point standard addition method (RHPSAM). Peak amplitudes at isoabsorptive point in ratio spectra were measured for determination of total concentrations of DIM and CIN. For subsequent determination of DIM concentration, difference between peak amplitudes at 250 nm and 267 nm were used in SCC. While the peak amplitude at 275 nm of the first derivative ratio spectra were used in S(1)DD; then subtraction of DIM concentration from the total one provided the CIN concentration. The last RHPSAM was a dual wavelength method in which two calibrations were plotted at 220 nm and 230 nm. The coordinates of intersection point between the two calibration lines were corresponding to DIM and CIN concentrations. The proposed methods were successfully applied for combined dosage form analysis, Moreover statistical comparison between the proposed and reported spectrophotometric methods was applied.

Analytical Eco-Scale for Assessing the Greenness of a Developed RP-HPLC Method Used for Simultaneous Analysis of Combined Antihypertensive Medications.

In the past few decades the analytical community has been focused on eliminating or reducing the usage of hazardous chemicals and solvents, in different analytical methodologies, that have been ascertained to be extremely dangerous to human health and environment. In this context, environmentally friendly, green, or clean practices have been implemented in different research areas. This study presents a greener alternative of conventional RP-HPLC methods for the simultaneous determination and quantitative analysis of a pharmaceutical ternary mixture composed of telmisartan, hydrochlorothiazide, and amlodipine besylate, using an ecofriendly mobile phase and short run time with the least amount of waste production. This solvent-replacement approach was feasible without compromising method performance criteria, such as separation efficiency, peak symmetry, and chromatographic retention. The greenness profile of the proposed method was assessed and compared with reported conventional methods using the analytical Eco-Scale as an assessment tool. The proposed method was found to be greener in terms of usage of hazardous chemicals and solvents, energy consumption, and production of waste. The proposed method can be safely used for the routine analysis of the studied pharmaceutical ternary mixture with a minimal detrimental impact on human health and the environment.

Comparative study of spectrophotometric methods manipulating ratio spectra: An application on pharmaceutical binary mixture of cinnarizine and dimenhydrinate

Four simple, specific, accurate and precise spectrophotometric methods are developed and validated for simultaneous determination of cinnarizine (CIN) and dimenhydrinate (DIM) in a binary mixture with overlapping spectra, without preliminary separation. The first method is dual wavelength spectrophotometry (DW), the second is a ratio difference spectrophotometric one (RD) which measures the difference in amplitudes between 250 and 270 nm of ratio spectrum, the third one is novel constant center spectrophotometric method (CC) and the fourth method is mean centering of ratio spectra (MCR). The calibration curve is linear over the concentration range of 4-20 and 10-45 μg/ml for CIN and DIM, respectively. These methods are tested by analyzing synthetic mixtures of the above drugs and they are applied to commercial pharmaceutical preparation of the subjected drugs. The validity of results was assessed by applying standard addition technique. The results obtained were found to agree statistically with those obtained by a reported method, showing no significant difference with respect to accuracy and precision.

Smart spectrophotometric methods based on normalized spectra for simultaneous determination of alogliptin and metformin in their combined tablets

Alogliptin (ALO) and metformin (MET) are coformulated for the treatment of type II diabetes mellitus. ALO is estimated at its λmax 277 nm (0D), while MET was determined accurately by four spectrophotometric methods with minimum manipulation steps based on normalized division spectrum namely; ratio difference, advanced amplitude modulation, first derivative ratio (1DD) and mean centering of the ratio spectra spectrophotometric methods. Linearity was acceptable over the concentration ranges of 5-40 and 2-16 μg/mL for ALO and MET, respectively. Accuracy and precision of the suggested methods were found to be within the acceptable limit. The specificity was inspected by analyzing laboratory prepared mixtures of the above drugs and their pharmaceutical preparation. The results of proposed and reported methods were statistically compared showing no significant difference regarding accuracy and precision. The developed methods could be applied for routine analysis of the cited drugs in quality control laboratories.

Application and validation of an eco-friendly TLC-densitometric method for simultaneous determination of co-formulated antihypertensive agents

Owing to the greater awareness that has arisen within the analytical community regarding the colossal negative influence of hazardous chemicals on both health and the environment, there is an increasing interest in developing more environment-friendly practices in different research areas. In this context, an eco-friendly TLC-densitometric method was designed, optimized and validated for the quantitative analysis of a ternary pharmaceutical mixture used for hypertension management, in the pure powdered form, synthetic mixtures and combined pharmaceutical formulation. The proposed method is based on the separation of the three co-formulated drugs; telmisartan (TL), hydrochlorothiazide (HZ) and amlodipine besylate (AM) on silica gel F254 plates, using green solvents as the developing system. The method was validated with regard to linearity, accuracy, precision, system suitability, and robustness. Comparison of the suggested method to the reported conventional TLC-densitometric method, regarding their validation parameters and greenness profiles, was carried out. The suggested method was found to be more eco-friendly and more solvent-/time-saving; hence it can be used for quality control analysis of the studied mixture in a safer way.

SELECTIVE CHROMATOGRAPHIC METHODS FOR THE DETERMINATION OF ROSUVASTATIN CALCIUM IN THE PRESENCE OF ITS ACID DEGRADATION PRODUCTS

Two accurate and sensitive stability-indicating methods for the determination of rosuvastatin calcium in the presence of its acid degradation products are presented. The first method utilizes quantitative spectrodensitometric evaluation thin-layer chromatography (TLC) of rosuvastatin calcium in the presence of its acid degradation products, using ethyl acetate/methanol/ammonia (7:3:0.01, by volume) as a mobile phase. Chromatograms are scanned at 245 nm. This method analyzes rosuvastatin calcium in a concentration range of 0.6–3.4 µg/band with mean percentage recovery of 99.78 ± 1.42. The second method is a high-performance liquid chromatography (HPLC) method for the simultaneous determination of rosuvastatin calcium in the presence of its acid degradation products. The mobile phase consists of water/acetonitrile/methanol (40:40:20, by volume). The standard curve of rosuvastatin calcium shows a good linearity over a concentration range of 10–60 µg mL−1 with mean percentage recovery of 100.22 ± 0.86. These methods were successfully applied to the determination of rosuvastatin calcium in bulk powder, laboratory-prepared mixtures containing different percentages of the acid degradation products, and pharmaceutical dosage forms. The validity of results was assessed by applying standard addition technique. The results obtained were found to agree statistically with those obtained by a reported method, showing no significant difference with respect to accuracy and precision.

Application and validation of superior spectrophotometric methods for simultaneous determination of ternary mixture used for hypertension management

Telmisartan (TL), Hydrochlorothiazide (HZ) and Amlodipine besylate (AM) are co-formulated together for hypertension management. Three smart, specific and precise spectrophotometric methods were applied and validated for simultaneous determination of the three cited drugs. Method A is the ratio isoabsorptive point and ratio difference in subtracted spectra (RIDSS) which is based on dividing the ternary mixture of the studied drugs by the spectrum of AM to get the division spectrum, from which concentration of AM can be obtained by measuring the amplitude values in the plateau region at 360nm. Then the amplitude value of the plateau region was subtracted from the division spectrum and HZ concentration was obtained by measuring the difference in amplitude values at 278.5 and 306nm (corresponding to zero difference of TL) while the total concentration of HZ and TL in the mixture was measured at their isoabsorptive point in the division spectrum at 278.5nm (Aiso). TL concentration is then obtained by subtraction. Method B; double divisor ratio spectra derivative spectrophotometry (RS-DS) and method C; mean centering of ratio spectra (MCR) spectrophotometric methods. The proposed methods did not require any initial separation steps prior the analysis of the three drugs. A comparative study was done between the three methods regarding their; simplicity, sensitivity and limitations. Specificity was investigated by analyzing the synthetic mixtures containing different ratios of the three studied drugs and their tablets dosage form. Statistical comparison of the obtained results with those found by the official methods was done, differences were non-significant in regard to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for TL, HZ and AM.