Simultaneous determination of fosinopril and hydrochlorothiazide in pharmaceutical formulations by spectrophotometric methods

Three new spectrophotometric procedures for the simultaneous determination of fosinopril and hydrochlorothiazide are described. The first method, derivative-differential spectrophotometry, comprised of measurement of the difference absorptivities derivatized in the first-order (ΔD₁) of a tablet extract in 0.1 N NaOH relative to that of an equimolar solution in methanol at wavelengths of 227.6 and 276.4 nm, respectively. The second method, depends on the application ratio spectra derivative spectrophotometric method to resolve the interferance due to spectral overlapping. The analytical signals were measured at 237.9, 243.8 nm for fosinopril and 262.4, 269.3 and 278.6 nm for hydrochlorothiazide in the binary mixture, in the first derivative of the ratio spectra of the mixture solutions in methanol. Calibration graphs were established for 4.0–50.0 μg ml⁻¹ fosinopril and 2.0–14.0 μg ml⁻¹ hydrochlorothiazide in binary mixture. The third method, absorbance ratio method, the determination of fosinopril and hydrochlorothiazide was performed by using the absorbances read at 210.0, 219.5 and 271.7 nm in the zero-order spectra of their mixture. The developed methods were compared with absorbance ratio method. Application of the suggested procedures were successfully applied to the determination of this compound in synthetic mixtures and in pharmaceutical preparations, with high percentage of recovery, good accuracy and precision.     

Stability-indicating methods for the determination of piretanide in presence of the alkaline induced degradates

Stability-indicating high performance liquid chromatography (HPLC), thin-layer chromatography (TLC) and first-derivative of ratio spectra (1DD) methods are developed for the determination of piretanide in presence of its alkaline induced degradates. HPLC method depends on separation of piretanide from its degradates on μ-Bondapak C₁₈ column using methanol:water:acetic acid (70:30:1, v/v/v) as a mobile phase at flow rate 1.0 ml/min and UV detector at 275 nm. TLC densitometic method is based on the difference in Rf-values between the intact drug and its degradates on thin-layer silica gel. Iso-propanol:ammonia 33% (8:2, v/v) was used as a developing mobile phase and the chromatogram was scanned at 275 nm. The derivative of ratio spectra method (1DD) depends on the measurement of the absorbance at 288 nm in the first-derivative of ratio spectra for the determination of the cited drug in the presence of its degradates. Calibration graphs of the three suggested methods are linear in the concentration ranges 0.02–0.3 μg/20 μl, 0.5–10 μg/spot and 5–50 μg/ml, with mean percentage recovery 99.27 ± 0.52, 99,17 ± 1.01 and 99.65 ± 1.01%, respectively. The three proposed methods were successfully applied for the determination of piretanide in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage form with good accuracy and precision. The results were statistically analyzed and compared with those obtained by the official method. Validation of the method was determined with favourable specificity, linearity, precision, and accuracy was assessed by applying the standard addition technique.     

Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods

Ratio spectra derivative spectrophotometry and two chemometric methods (classical least squares, CLS and inverse least squares, ILS, were proposed for the simultaneous quantitative analysis of a binary mixture consists of cyproterone acetate (CA) and estradiol valerate (EV) in the commercial pharmaceutical preparations. In the ratio spectra derivative method, linear regression equations for both drugs were obtained by measuring the analytical signals at the wavelenghts corresponding to either maximums and minimums in the first derivative spectra of the ratio spectra. In the chemometric techniques, the concentration matrix was prepared by using the synthetic mixtures containing these drugs. The absorbance matrix corresponding to the concentration matrix was obtained by measuring the absorbances at 14 wavelengths in the range 220-290 nm for the zero-order spectra. Two chemometric calibrations were constructed by using the absorbance matrix and concentration matrix for the prediction of the unknown concentrations of CA and EV in their mixture. The numerical values were calculated by using 'MAPLE V' software. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing these two drugs. The proposed methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.     

Simultaneous spectrophotometric determination of pseudoephedrine hydrochloride and ibuprofen in a pharmaceutical preparation using ratio spectra derivative spectrophotometry and multivariate calibration techniques

Spectrophotometric methods are described for the simultaneous determination of pseudoephedrine hydrochloride and ibuprofen in their combination. The obtained data were evaluated by using five different methods. In the first method, ratio spectra derivative spectrophotometry, analytical signals were measured at the wavelengths corresponding to either maximums and minimums for both drugs in the first derivative spectra of the ratio spectra obtained by using each other spectra as divisor in their solution in 0.1 M HCl. In the other four spectrophotometric methods using chemometric techniques, classical least-squares, inverse least-squares, principal component regression and partial least-squares (PLS), the concentration data matrix were prepared by using the synthetic mixtures containing these drugs in methanol:0.1 M HCl (3:1). The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 240-285 nm in the intervals with deltalambda = 2.5 nm at 18 wavelengths in their zero-order spectra, then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of pseudoephedrine hydrochloride and ibuprofen in their mixture. The procedures did not require any separation step. The linear range was found to be 300-1300 microg/ml for ibuprofen and 100-1300 microg/ml for pseudoephedrine hydrochloride in all five methods. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures. The five methods were successfully applied to tablets and the results were compared with each other.     

Simultaneous spectrophotometric determination of chlorphenoxamine hydrochloride and caffeine in a pharmaceutical preparation using first derivative of the ratio spectra and chemometric methods

Three new methods are described for the simultaneous determination of chlorphenoxamine hydrochloride (CP) and caffeine (CAF) in their combination. In the first method, ratio spectra derivative spectrophotometry, analytical signals were measured at the wavelengths corresponding to either maxima and minima for both drugs in the first derivative spectra of the ratio spectra obtained by using each other spectra as divisor in their solution in 0.1 M HCl. In the other two methods, chemometric techniques, classical least-squares (CLS) and inverse least-squares (ILS), the concentration data matrix were prepared by using the synthetic mixtures containing these drugs in 0.1 M HCl. The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 225-285 nm in the intervals with Deltalambda = 5 nm at 13 wavelengths in their zero-order spectra, then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of CP and CAF in their mixture. The numerical values were calculated by using MAPLE V software in chemometric methods. The procedures do not require any separation step. The accuracy and the precision of the methods have been determined and they have been validated by analyzing synthetic mixtures containing title drugs. These three methods were successfully applied to a pharmaceutical formulation, sugar-coated tablet, and the results were compared with each other.     

Simultaneous Derivative Spectrophotometric Analysis of Doxylamine Succinate, Pyridoxine Hydrochloride and Folic Acid in Combined Dosage Forms

Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot''s method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 μg/ml, 1-40 μg/ml and 1-30 μg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.     

Spectrophotometric quantitative determination of cilazapril and hydrochlorothiazide in tablets by chemometric methods

Four chemometric methods were applied to simultaneous determination of cilazapril and hydrochlorothiazide in tablets. Classical least-square (CLS), inverse least-square (ILS), principal component regression (PCR) and partial least-squares (PLS) methods do not need any priori graphical treatment of the overlapping spectra of two drugs in a mixture. For all chemometric calibrations a concentration set of the random mixture consisting of the two drugs in 0.1 M HCI and methanol (1:1) was prepared. The absorbance data in the UV-Vis spectra were measured for the 15 wavelength points (from 222 to 276 nm) in the spectral region 210-290 nm considering the intervals of deltalambda = 4 nm. The calibration of the investigated methods involves only absorbance and concentration data matrices. The developed calibrations were tested for the synthetic mixtures consisting of two drugs and using the Maple V software the chemometric calculations were performed. The results of the methods were compared each other as well as with HPLC method and a good agreement was found.     

Chemometric resolution of a mixture containing hydrochlorothiazide and amiloride by absorption and derivative spectrophotometry

Four chemometric techniques, classical least squares (CLS) and inverse least squares (ILS) and principal component regression (PCR) and partial least squares regression (PLSR) were applied to the absorption and derivative spectrophotometric determinations of amiloride and hydrochlorothiazide in a pharmaceutical preparation. Four chemometric calibrations for both zero-order and first derivative spectra were constructed by measuring the absorbance and their dA/dlambda values at 34 points in the wavelength range 205-395 nm for a training set containing 2-10 microg/ml amiloride and 4-28 microg/ml hydrochlorothiazide corresponding to 25 point mixture design. The building chemometric calibrations were confirmed by using the synthetic mixtures containing two drugs. The results obtained by the proposed techniques based on the use of the measurements at the absorption spectra and at the first derivative spectra were statistically compared with each other.     

Determination of some aminobenzoic acid derivatives: glafenine and metoclopramide

Simple, sensitive and accurate spectrophotometric methods for the determination of glafenine and metoclopramide hydrochloride are described. The first method is based on the oxidation of glafenine with iodic acid in strong acid medium to give a coloured diphenylbenzidine derivative and subsequent measurement of the coloured product at 509 nm. Beer's law is obeyed over the concentration range 2.5–20 μg ml⁻¹. The second method depends on the interaction of metoclopramide hydrochloride with p-dimethylaminocinnamaldehyde, to give a red coloured schiff's base with an absorbance maximum at 548 nm. Obedience to Beer's law is achieved over the concentration range 5–30 μg ml⁻¹. First-derivative method is used to overcome the slight interference of p-dimethylaminocinnamaldehyde reagent blank at the wavelength of measurement. Linearity between the peak heights at 576 nm versus concentration range 5–25 μg ml⁻¹ metoclopromide hydrochloride is obtained. The proposed methods have been successfully applied to the determination of these drugs in commercial products without interference. The validity of the methods is assessed by applying the standard addition technique, the relative standard deviation is less than 1%. The proposed methods are compared with reference methods with good agreement.     

Stability-indicating methods for the determination of sumatriptan succinate

Four stability-indicating methods were developed for the determination of sumatriptan succinate in the presence of its degradation products. The first method depends on the quantitative densitometric evaluation of thin-layer chromatography of sumatriptan succinate in the presence of its degradation products without any interference. Cyclohexane–dichloromethane–diethylamine (50:40:10 v/v/v) was used as a mobile phase and the chromatogram was scanned at 228 nm. This method determines sumatriptan succinate in the concentration range l–8 μg per spot with mean percentage recovery 100.52±1.23%. The second and third methods depend on the use of first-derivative (D₁) and second-derivative (D₂) spectrophotometry at 234 and 238 nm, respectively. These methods determine the drug in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 99.91±1.01% and 99.96±1.13% for (D₁) and (D₂), respectively. The fourth method depends on the use of ratio derivative spectrophotometric technique. The amplitude in the first derivative of the ratio spectra at 235 nm was selected to determine the cited drug in the presence of its degradation products. Calibration graph is linear in the concentration range 1.25–10 μg ml⁻¹ with mean percentage recovery 100.19±1.19%. The suggested methods were successfully applied for determining sumatriptan succinate in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (Imigran tablet) with good accuracy and precision. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method.     

Simultaneous spectrophotometric determination of diclofenac potassium and methocarbamol in binary mixture using chemometric techniques and artificial neural networks

In this study, the simultaneous determination of diclofenac potassium (DP) and methocarbamol (MT) by chemometric approaches and artificial neural networks using UV spectrophotometry has been reported as a simple alternative to using separate models for each component. Three chemometric techniques-classical least-squares (CLS), principal component regression (PCR), and partial least-squares (PLS)-along with radial basis function-artificial neural network (RBF-ANN) were prepared by using the synthetic mixtures containing the two drugs in methanol. A set of synthetic mixtures of DP and MT was evaluated and the results obtained by the application of these methods were discussed and compared. In CLS, PCR, and PLS, the absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbances in the range 260-310 nm in the intervals with Δλ = 0.2 nm in their zero-order spectra. Then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of DP and MT in their mixtures. In RBF-ANN, the input layer consisting of 251 neurons, 9 neurons in the hidden layer, and 2 output neurons were found appropriate for the simultaneous determination of DP and MT. The accuracy and the precision of the four methods have been determined and they have been validated by analyzing synthetic mixtures containing the two drugs. The proposed methods were successfully applied to a pharmaceutical formulation containing the examined drugs.     

Simultaneous determination of valsartan and hydrochlorothiazide in tablets by first-derivative ultraviolet spectrophotometry and LC

First-derivative ultraviolet spectrophotometry and high-performance liquid chromatography (HPLC) were used to determine valsartan and hydrochlorothiazide simultaneously in combined pharmaceutical dosage forms. The derivative procedure was based on the linear relationship between the drug concentration and the first derivative amplitudes at 270.6 and 335 nm for valsartan and hydrochlorothiazide, respectively. The calibration graphs were linear in the range of 12.0–36.1 μg ml⁻¹ for valsartan and 4.0–12.1 μg ml⁻¹ for hydrochlorothiazide. Furthermore, a high- performance liquid chromatographic procedure with ultraviolet detection at 225 nm was developed for a comparison method. For the HPLC procedure, a reversed phase column with a mobile phase of 0.02 M phosphate buffer (pH 3.2)-acetonitrile (55: 45; v/v), was used to separate for valsartan and hydrochlorothiazide. The plot of peak area ratio of each drug to the internal standard versus the respective concentrations of valsartan and hydrochlorothiazide were found to be linear in the range of 0.06–1.8 and 0.07–0.5 μg ml⁻¹, respectively. The proposed methods were successfully applied to the determination of these drugs in laboratory-prepared mixtures and commercial tablets.     

A comparison of matrix resolution method, ratio spectra derivative spectrophotometry and HPLC method for the determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparation

A comparison of two spectrophotometric methods and a HPLC method were described in this work for the analysis of pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination. In the first method, A₁¹ (1%, 1 cm) values of these two compounds were calculated using absorbances measured at 246.8 and 290.5 nm in zero-order spectra. The matrix was written for A₁¹ (1%, l cm) values and the concentration of both compounds were determined using ‘Matlab’ software. In the second method, the measurements in the derivative of the ratio spectra were made at 297.8 and 309.5 nm for pyridoxine hydrochloride and at 245.6 and 257.7 nm for thiamine hydrochloride. The calibration graphs were established in the range 8–40 μg/ml of both vitamins. In the HPLC method, the separation of these compounds was realized on a Nucleosil 100-5 C₁₈ column with 0.1 M (NH₄)₂C0₃–water–methanol (5:15:80 v/v) as the mobile phase. Results of spectrophotometric and HPLC procedures were compared.     

Stability indicating methods for the determination of loratadine in the presence of its degradation product

Four stability-indicating procedures have been suggested for determination of the non sedating antihistaminic agent loratadine. Loratadine being an ester undergoes alkaline hydrolysis and the corresponding acid derivative is produced as a degradation product. Its identity was confirmed using IR and MS. The first procedure is based on determination of loratadine by HPLC with detection at wavelength, 250 nm. Mobile phase is acetonitrile:orthophosphoric acid (35:65) using benzophenone as an internal standard. Sensitivity range is 5.00–50.00 μg/ml. Second determination is a densitometric procedure based on determination of loratadine in the presence of its degradate at λ 246 nm using the mobile phase; methanol:ammonia (10:0.15). Sensitivity range is 1.25–7.50 μg per spot. The third procedure is a spectrophotometric one where a mixture of loratadine and its degradate are resolved by first derivative ratio spectra. Sensitivity range is found to be 3.00–22.00 μg/ml, upon carrying out the measurements at wavelengths 236, 262.4 and 293.2 nm. The fourth procedure is based on second derivative spectrophotometry, where D₂ measurements are carried out at λ 266 nm. The sensitivity range is 3.00–22.00 μg/ml. The validity of the described procedures was assessed by applying the standard addition technique. Statistical analysis of the results have been carried out revealing high accuracy and good precision. The suggested procedures could be used for determination of loratadine both in pure and dosage forms, as well as in the presence of its degradate.     

Simultaneous determination of paracetamol and methocarbamol in tablets by ratio spectra derivative spectrophotometry and LC

The application of the ratio spectra derivative spectrophotometry and high-performance liquid chromatography (HPLC) to the simultaneous determination of paracetamol (PAR) and methocarbamol (MET) in combined pharmaceutical tablets is presented. The spectrophotometric procedure is based on the use of the first derivative of the ratio spectra obtained by dividing the absorbtion spectrum of the binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes were measured at 243.0 and 230.3 nm for the assay of PAR and MET, respectively. Calibration graphs were established for 2-30 microg ml for PAR and 2-36 microg/ml for MET in binary mixture. The detection limits for PAR and MET were found 0.097 and 0.079 microg/ml, respectively; while the quantification limits were 0.573 microg/ml for PAR and 1.717 microg/ml for MET. For the HPLC procedure, a reversed-phase column with a mobile phase of methanol-water (60:40, v/v), was used to separate both compounds with a detection of 274.0 nm. Linearity was obtained in the concentration range of 2 300 and 1.5-375 microg/ml for PAR and MET, respectively. The detection and quantification limits were found to be 0.42 and 1.4 microg/ml for PAR and 0.36 and 1.2 microg/ml for MET, respectively. The relative standard deviations were found to be less than 0.52%, indicating reasonable repeatibility of both methods. The proposed methods were successfully applied to the determination of these drugs in commercial tablets.     

Simultaneous high performance liquid chromatographic and derivative ratio spectra spectrophotometry determination of chlorpheniramine maleate and phenylephrine hydrochloride

Rapid, precise, accurate and specific high performance liquid chromatographic and derivative ratio spectra spectrophotometry procedures are described for the simultaneous analysis of chlorpheniramine maleate and phenylephrine hydrochloride in combined pharmaceutical dosage forms. The chromatographic methods were standardised using a LiChrosorb RP- C₁₈ column (5 μm , 20 cm × 4.6 mm), UV detection at 269.0 nm and mobile phases consisting of methanol/phosphate buffer (50 ml 0.2 M monobasic potassium phosphate (KH₂PO₄) + 34.7 ml 0.2 M NaOH; 70:30, apparent pH 7.2). Using derivative ratio spectra spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 238.9 and 280.0 nm were selected to determine chlorpheniramine maleate and phenylephrine hydrochloride in the mixture. Commercial nasal drops and laboratory-prepared mixtures containing both drugs in different proportions were assayed using the methods developed. Both methods showed good linearity, precision and reproducibility.     

Dissolution and assaying of multicomponent tablets by chemometric methods using computer-aided spectrophotometer

Dissolution of three component tablets containing paracetamol (APAP), propyphenazone (PP), and caffeine (CAF) was carried out by USP paddle method. Three chemometric methods; inverse least square (ILS), principal component regression (PCR) and partial least squares (PLS) were applied to simultaneous assay of APAP, PP and CAF in tablets. The PCR, PLS and ILS methods were applied to simultaneous dissolution APAP, PP and CAF in tablets using a double beam UV-Vis spectrophotometer without any chemical separation and any graphical treatment of the overlapping spectra of three drugs. Twenty two mixture solutions in different concentrations were prepared in simulated gastric juice (SGJ, USP) for the chemometric calibrations as training set. The absorbance data matrix was obtained by measuring the absorbance at 14 wavelength points (from 222.5 to 292.5 nm) with the intervals of 5 nm (Deltalambda=5 nm) in the spectral region between 200 and 310 nm. Training set and absorbance data were used for the calibrations of chemometric methods. The developed calibrations were tested for the previously prepared solutions of mixture of three drugs for the validation of the assay method. The chemometric calculations were performed by using the 'MAPLE VRSQUO; software. The results of three chemometric methods were statistically compared with each other. These chemometric calibrations were successfully applied to the content uniformity and dissolution of the multicomponent tablets without any separation procedure. The synthetic mixtures of three drugs were used for the validity of the calibrations. Means recoveries (percent) and relative standard deviation of PLS, PCR and ILS methods were found to be 100.1+/-0.6, 101.4+/-1.6 and 100.1+/-0.6 for APAP; 100.9+/-3.2, 102.0+/-3.3 and 100.9+/-3.2 for PP; 99.9+/-3.5, 101.6+/-3.3 and 99.9+/-3.2 for CAF, respectively. Dissolution profiles of three component tablets were performed. More than 95% of drugs were dissolved within 15 min. All of the three-chemometric methods in this study can be satisfactorily used for the quantitative analysis and for dissolutions test of multicomponent dosage form.     

Simultaneous quantitative determination of salbutamol sulfate and bromhexine hydrochloride in drug preparations by difference spectrophotometry

A difference spectrophotometric procedure has been developed for the simultaneous determination of salbutamol sulfate (SS) and bromhexine hydrochloride (BH) in tablet preparations. The method comprised the measurements of the absorbance of a solution of the drug mixture in pH 2.0 buffer solution relative to that of an equimolar solution in 0.1 N methanolic NaOH at wavelengths of 310 and 280 nm. The presence of identical isosbestic points for pure drug solutions and sample solutions indicated the non-interference of excipients in the absorption at these wavelengths. Compliance with Beer's law was achieved in the concentration range of 0–100 μg/ml for SS and 0–200 μg/ml for BH at these wavelengths.     

Spectrophotometric determination of pefloxacin in pharmaceutical preparations

It has been established that the antibiotic pefloxacin (Abaktal) methane-sulphonate reacts with Fe(III) at pH 1.00–8.00 to form a water-soluble complex with maximum absorbance at 360 nm. The composition of the complex, determined spectrophotometrically by the application of Job's, molar-ratio and Bent—French's methods, was pefloxacin: Fe(III) = 1:1 (pH = 2.50; λ = 360 nm; μ = 0.1 M). The relative stability constant, obtained by the methods of Sommer and Asmus was 10^5.02 (pH = 2.50; λ = 360 nm; μ = 0.1 M). The molar absorptivity of the complex at 360 nm was found to be 4.8 × 10³ l mol⁻¹ cm⁻¹, Beer's law was followed for pefloxacin concentrations of 2.15–85.88 μg ml⁻¹. The lower sensitivity limit of the method was 2.15 μg ml⁻¹. The relative standard deviation (n = 10) was 0.57–1.07%. The method can be applied to the rapid and simple determination of pefloxacin in aqueous solutions and tablets.     

UV and Three Derivative Spectrophotometric Methods for Determination of Ezetimibe in Tablet Formulation

UV, first, second and third derivative spectrophotometric methods have been developed for the determination of ezetimibe in pharmaceutical formulation. The solutions of standard and sample were prepared in methanol. For the first method, UV spectrophotometry, the quantitative determination of the drug was carried at 233 nm and the linearity range was found to be 6-16 μg/ml. For the first, second and third derivative spectrophotometric methods the drug was determined at 259.5 nm, 269 nm and 248 nm with the linearity ranges 4-14 μg/ml, 4-14 μg/ml and 4-16 μg/ml. The calibration graphs constructed at their wavelength of determination were found to be linear for UV and derivative spectrophotometric methods. All the proposed methods have been extensively validated. The described methods can be readily utilized for the analysis of pharmaceutical formulation. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations.