Stability-indicating Spectrophotometric Methods Research Articles

Two different spectrophotometric methods for simultaneous determination of binary mixture of atenolol and amlodipine in commercial formulation

Two different spectrophotometric methods for simultaneous determination of binary mixture of atenolol and amlodipine in commercial formulation

Evaluation of the Efficiency of Smart Stability-Indicating Spectrophotometric Methods Based on Mathematical and Statistical Processing of the Obtained Results Via Different Manipulating Pathways

Background: Smart different stability-indicating spectrophotometric methods have been established for the assay of chlordiazepoxide and clidinium bromide without the intervention of alkaline degradate of clidinium via various and different manipulating pathways without previous separation steps. Objective: The specificity of the established methods was inspected by analysing mixtures of cited drugs in the existence of the alkali-induced degradation product. Methods: These methods were employed either on scanned zero-order absorption spectra using absorbance subtraction, dual wavelength and Q-absorbance ratio or the amplitudes of the ratio spectra of zero-order absorption spectra like amplitude modulation and by derivative techniques to the ratio spectra as a derivative ratio method. In addition, the absorbance of the recovered zero-order absorption spectra was applied by successive ratio subtraction coupled with constant multiplication. Finally, the pathway depends on the amplitudes of the derivative spectra, successive derivative subtraction coupled with constant multiplication. The ranges of linearity were (1-12µg/mL) for chlordiazepoxide and (3- 12µg/mL) for clidinium bromide. Results: The outcomes achieved by the prospective methods were in consent with those of the official and reported methods when statistically compared using student’s t test, F-test and one-way ANOVA where no significant difference was detected with suitable precision, proving the absence of any important difference in accuracy and precision between them. They were confirmed in accordance with International Conference on Harmonization guidelines. Conclusion: The established methods can be considered as alternative methods for the routine determination of this fixed dose combination with minimum sample preparation.

Different aspects in manipulating overlapped spectra used for the analysis of trimebutine maleate and structure elucidation of its degradation products

BackgroundFour rapid, accurate, and validated stability-indicating spectrophotometric methods have been described in the present work for the analysis of trimebutine maleate (TM) in existence of its degradation products in its authentic form and in pharmaceutical formulations excluding any separation steps.ResultsThese methods were a dual-wavelength (DW) method which allows the determination of TM in existence of its degradation products at 243 nm and 269 nm, second derivative (D2) method measured at peak amplitude at 268 nm, ratio difference (RD) method at 242 nm and 278 nm, and constant center coupled with spectrum subtraction (CC-SS) method at 242 nm and 278 nm versus 278 nm. By applying the suggested methods, TM could be quantified in the range of 5.0–60.0 μg/mL with percentage recoveries 99.97 ± 0.40, 100.36 ± 0.58, 99.90 ± 0.42, and 100.15 ± 0.45 for DW, D2, RD, and CC-SS methods, respectively. International Conference on Harmonization guidelines were followed for validation of the described methods, and the application of laboratory-prepared mixtures along with different pharmaceutical drugs including the target drug showed favorable results without any contribution from additives.ConclusionsStatistical comparison was used to compare the proposed and official methods, and satisfactory results for both accuracy and precision were obtained. The results confirm the applicability of the suggested methods for the determination of TM in quality control laboratories.

Two-wavelength manipulation stability-indicating spectrophotometric methods for determination of meropenem and ertapenem: greenness consolidation and pharmaceutical product application

Green assessed, UV-spectrophotometric methods were developed and validated for estimation of meropenem (MP) and ertapenem (EP), categorized to be non-classical β-lactam antibiotics, in the presence of their corresponding oxidative and hydrolytic degradants. The methods were successful to be used as stability-indicating ones and be applied for determination of the cited compounds in drug product and in pharmaceutical formulations. Three different spectrophotometric methods concerning two wavelengths manipulation for drug-degradant mixture resolution were adopted, namely; dual and induced dual wavelength, ratio difference, and advanced amplitude centering for partially overlapping spectra. Testing of the methods selectivity was achieved by successful analysis of synthetic mixtures of the studied drugs with different degradants. Validation was performed according to the USP guidelines. Application to pharmaceutical formulations and standard addition technique proved the methods’ analytical performance. Statistical comparison of the obtained results with those of the official or reported HPLC methods was performed using student t test, F test, and one-way ANOVA, where no significant differences with respect to accuracy and precision were observed. The greenness evaluation of the developed methods was assessed by applying two metrics to ensure environmental and personnel safety. No prior separation or long preparation steps were required for the proposed methods. The developed methods were specific, cost effective, and environmentally safe, less time-consuming methods for the quantitative determination of MP and EP in quality control laboratories with acceptable ultra-micro-linearity ranges and a promising wider applicability.

Stability-Indicating Spectrophotometric Methods for Determination of Milnacipran HCl and Duloxetine HCl in Bulk Drug and Pharmaceutical Formulations

The present study describes accurate and sensitive stability-indicating spectrophotometric methods for the determination of Milnacipran HCl in presence of its acid, base degradates, and Duloxetine HCl in presence of its base degradates; including Dual-wavelength, Ratio difference, and Ratio derivative techniques. The developed methods were validated according to the International Conference on Harmonisation (ICH) guidelines. The recovery percentage of Milnacipran HCl and Duloxetine HCl were found to be in the ranges 99.42-100.42% and 100.17-100.3%, respectively. The low relative standard deviation of precision results confirms the suitability of the proposed methods for the estimation of the studied drugs in pure form, laboratory-prepared mixtures, and pharmaceutical formulations. Statistical comparison of the proposed methods with the reported methods revealed that there were no significant differences concerning the accuracy and precision of the adopted techniques. Validation studies demonstrated that the proposed methods are easy, specific, and rapid for the determination of Milnacipran HCl and Duloxetine HCl.

Validated stability-indicating spectrophotometric methods for the determination of Silodosin in the presence of its degradation products

Five simple, rapid, accurate, and precise spectrophotometric methods are developed for the determination of Silodosin (SLD) in the presence of its acid induced and oxidative induced degradation products. Method A is based on dual wavelength (DW) method; two wavelengths are selected at which the absorbance of the oxidative induced degradation product is the same, so wavelengths 352 and 377 nm are used to determine SLD in the presence of its oxidative induced degradation product. Method B depends on induced dual wavelength theory (IDW), which is based on selecting two wavelengths on the zero-order spectrum of SLD where the difference in absorbance between them for the spectrum of acid induced degradation products is not equal to zero so through multiplying by the equality factor, the absorption difference is made to be zero for the acid induced degradation product while it is still significant for SLD. Method C is first derivative (1D) spectrophotometry of SLD and its degradation products. Peak amplitudes are measured at 317 and 357 nm. Method D is ratio difference spectrophotometry (RD) where the drug is determined by the difference in amplitude between two selected wavelengths, at 350 and 277 nm for the ratio spectrum of SLD and its acid induced degradation products while for the ratio spectrum of SLD and its oxidative induced degradation products the difference in amplitude is measured at 345 and 292 nm. Method E depends on measuring peak amplitudes of the first derivative of the ratio (1DD) where peak amplitudes are measured at 330 nm in the presence of the acid induced degradation product and measured by peak to peak technique at 326 and 369 nm in the presence of the oxidative induced degradation product. The proposed methods are validated according to ICH recommendations. The calibration curves for all the proposed methods are linear over a concentration range of 5–70 μg/mL. The selectivity of the proposed methods was tested using different laboratory prepared mixtures of SLD with either its acid induced or oxidative induced degradation products showing specificity of SLD with accepted recovery values. The proposed methods have been successfully applied to the analysis of SLD in pharmaceutical dosage forms without interference from additives.

Stability Indicating Spectrophotometric Methods for the Determination of Cefoxitin Sodium in Pure form and in Pharmaceutical Preparations

Four simple, accurate and precise stability-indicating spectrophotometric methods were developed and validated for the simultaneous determination of cefoxitin sodium in presence of its alkaliinduced degradation product without prior separation namely; Q-analysis, absorbance subtraction, absorbance ratio, and amplitude modulation. These methods were validated for accuracy and precision. The four proposed methods were successfully applied for the determination of the cited drug in pure form and in pharmaceutical preparation also in the presence of its alkaline degradation product. The obtained results were statistically compared with those of a reported method. The comparison showed that there are no significant differences between the proposed methods and the reported method.

Determination of Cefoxitin Sodium in the Presence of Its Alkali-induced Degradation Product Through Different Ratio Spectra Manipulating Methods

Four simple, accurate and precise stability-indicating spectrophotometric methods manipulating ratio spectra were introduced for determination of cefoxitin sodium in presence of its alkali-induced degradation product without prior separation more specifically; ratio difference, ratio derivative, mean centering and ratio subtraction. The methods were validated for accuracy, precision. The four proposed methods were successfully applied for the determination of cefoxitin sodium in pure form and in its pharmaceutical preparation. Results obtained were statistically analyzed and compared with those of a reported method, no significant differences between the proposed methods and the reported method.

Development and Validation of Stability-Indicating Derivative Spectrophotometric Methods for Determination of Dronedarone Hydrochloride

Rapid, sensitive, cost effective and reproducible stability-indicating derivative spectrophotometric methods have been developed for the estimation of dronedarone HCl employing peak–zero (P–0) and peak–peak (P–P) techniques, and their stability-indicating potential assessed in forced degraded solutions of the drug. The methods were validated with respect to linearity, accuracy, precision and robustness. Excellent linearity was observed in concentrations 2–40 μg/ml (r 2 = 0.9986). LOD and LOQ values for the proposed methods ranged from 0.42–0.46 μg/ml and 1.21–1.27 μg/ml, respectively, and excellent recovery of the drug was obtained in the tablet samples (99.70 ± 0.84%).

Development and Validation of Stability Indicating Spectrophotometric Methods for Determination of Sulbutiamine in Tablet Dosage Form

Five sensitive, selective and precise stability-indicating spectrophotometric methods for the determination of Sulbutiamine (SUL) in the presence of its alkali-induced degradation product (DEG) were developed and validated. Method A is differential dual wavelength (D1DWL) applied in the analysis of SUL in binary mixture via its first derivative spectra using the difference between two points with equal amplitudes in the alkali-induced degradation product, thus DEG acts as zero contribution. Method B is second derivative spectrophotometry (D2), which allowed the determination of SUL at 300.0 nm. Method C is second derivative of the ratio spectra (DD2) in which SUL was determined by measuring the peak amplitude at 301.0 nm. Method D is the ratio difference spectrophotometry (RD), where the difference between amplitudes of the absorbance ratio spectra at 237.2 and 274.0 nm were recorded and Method E; Ratio subtraction (RSM) where the zero order spectra of pure SUL were extracted from their laboratory prepared mixtures, and consequently SUL can be analyzed at its maxima. The linearity for SUL was obtained within concentrations ranging from 5.00 - 50.00 μg/mL with percentage recovery of 100.58 ± 0.98, 99.62 ± 1.16, 100.70 ± 1.38, 100.06 ± 1.00 and 99.56 ± 1.00 for the five methods, respectively.

Stability-indicating spectrophotometric methods for determination of the anticoagulant drug apixaban in the presence of its hydrolytic degradation product

Apixaban (a novel anticoagulant agent) was subjected to a stress stability study including acid, alkali, oxidative, photolytic, and thermal degradation. The drug was found to be only liable to acidic and alkaline hydrolysis. The degradation product was then isolated and identified by IR and GC–mass spectrometry. Four spectrophotometric methods, namely; first derivative (D1), derivative ratio (DR), ratio difference (RD) and mean centering of ratio spectra (MCR), have been suggested for the determination of apixaban in presence of its hydrolytic degradation product. The proposed methods do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined, and the methods were validated as per ICH guidelines and the specificity was assessed by analyzing synthetic mixtures containing different percentages of the degradation product with the drug. The developed methods were successfully applied for the determination of apixaban in bulk powder and its tablet dosage form.

Different approaches in manipulating ratio spectra applied for the analysis of Cefprozil in presence of its alkaline-induced degradation product: A comparative study

Four simple, accurate and precise stability-indicating spectrophotometric methods manipulating ratio spectra were developed and validated for simultaneous determination of Cefprozil (CZ) and its alkaline-induced degradation product (DCZ) without prior separation namely; ratio difference, mean centering, derivative ratio using Savitsky–Golay filter and continuous wavelet transform. The accuracy, precision and linearity ranges of the proposed methods were determined. The methods were validated and the specificity was assessed by analyzing synthetic mixtures containing the drug and its degradate. The four methods were applied for the determination of the cited drug in tablets and the obtained results were statistically compared with those of a reported method. The comparison showed that there are no significant differences between the proposed methods and the reported method regarding both accuracy and precision.

Stability-indicating liquid chromatographic and UV spectrophotometric methods for the quantification of ciprofibrate in capsules and tablets

This study describes the development and evaluation of stability-indicating liquid chromatographic (LC) and UV spectrophotometric methods for the quantification of ciprofibrate (CPF) in tablets and capsules. Isocratic LC separation was achieved on a RP18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 3.0 with triethylamine (10% v/v) and acetonitrile (35:65 v/v), with a flow rate of 1.0 mL min-1. Detection was achieved with a photodiode array detector at 233 nm. For the spectrophotometric analysis, ethanol and water were used as the solvent and a wavelength of 233 nm was selected for the detection. The methods were validated according to International Conference on Harmonization (ICH) guidelines for validating analytical procedures. Statistical analysis showed no significant difference between the results obtained by the two methods. The proposed methods were successfully applied to the CPF quality-control analysis of tablets and capsules.

Validated stability-indicating spectrophotometric methods for the determination of cefixime trihydrate in the presence of its acid and alkali degradation products.

Five simple, accurate, precise, and economical spectrophotometric methods have been developed for the determination of cefixime trihydrate (CFX) in the presence of its acid and alkali degradation products without prior separation. In the first method, second derivative (2D) and first derivative (1D) spectrophotometry was applied to the absorption spectra of CFX and its acid (2D) or alkali (1D) degradation products by measuring the amplitude at 289 and 308 nm, respectively. The second method was a first derivative (1DD) ratio spectrophotometric method where the peak amplitudes were measured at 311 nm in presence of the acid degradation product, and 273 and 306 nm in presence of its alkali degradation product. The third method was ratio subtraction spectrophotometry where the drug is determined at 286 nm in laboratory-prepared mixtures of CFX and its acid or alkali degradation product. The fourth method was based on dual wavelength analysis; two wavelengths were selected at which the absorbances of one component were the same, so wavelengths 209 and 252 nm were used to determine CFX in presence of its acid degradation product and 310 and 321 nm in presence of its alkali degradation product. The fifth method was bivariate spectrophotometric calibration based on four linear regression equations obtained at the wavelengths 231 and 290 nm, and 231 and 285 nm for the binary mixture of CFX with either its acid or alkali degradation product, respectively. The developed methods were successfully applied to the analysis of CFX in laboratory-prepared mixtures and pharmaceutical formulations with good recoveries, and their validation was carried out following the International Conference on Harmonization guidelines. The results obtained were statistically compared with each other and showed no significant difference with respect to accuracy and precision.

A sensitive and specific high-performance thin-layer chromatography-densitometry method for determination of Rebamipide in the bulk material and in pharmaceutical formulation

Rebamipide (RBP), α((4-chlorobenzoyl)-amino)-1,2-dihydro-2-oxo-4-quinoline propanoic acid is antiulcer (gastric cytoprotectant). Literature survey revealed many reverse-phase high-performance liquid chromatography (RP-HPLC) methods for determination of RBP in human plasma, rat plasma, and coionic tissue. Stability-indicating liquid chromatographic assay method and first-order derivative spectrophotometric methods have been established for the determination of RBP in bulk and tablet dosage form. Nowadays, high-performance thin-layer chromatography (HPTLC) is becoming a routine analytical technique due to its low operating cost, high sample throughput, and need for minimum sample clean up. The major advantage of HPTLC is that several samples can be run simultaneously using a small quantity of mobile phase unlike HPLC, thus lowering analysis time and cost per analysis. The intention of the present work is to establish simple, precise, and accurate stability-indicating densitometric thin-layer chromatography (TLC)-densitometry method for analysis of RBP in the bulk material and in tablets. Further the developed method has to be validated as per the International Conference on Harmonisation (ICH) guidelines.

Smart Stability-Indicating Spectrophotometric Methods for Determination of Binary Mixtures Without Prior Separation

Ratio subtraction and isosbestic point methods are 2 innovating spectrophotometric methods used to determine vincamine in the presence of its acid degradation product and a mixture of cinnarizine (CN) and nicergoline (NIC). Linear correlations were obtained in the concentration range from 8-40 microg/mL for vincamine (I), 6-22 microg/mL for CN (II), and 6-36 microg/mL for NIC (III), with mean accuracies 99.72 +/- 0.917% for I, 99.91 +/- 0.703% for II, and 99.58 +/- 0.847 and 99.83 +/- 1.039% for III. The ratio subtraction method was utilized for the analysis of laboratory-prepared mixtures containing different ratios of vincamine and its degradation product, and it was valid in the presence of up to 80% degradation product. CN and NIC in synthetic mixtures were analyzed by the 2 proposed methods with the total content of the mixture determined at their respective isosbestic points of 270.2 and 235.8 nm, and the content of CN was determined by the ratio subtraction method. The proposed method was validated and found to be suitable as a stability-indicating assay method for vincamine in pharmaceutical formulations. The standard addition technique was applied to validate the results and to ensure the specificity of the proposed methods.

Stability-Indicating Spectrophotometric and Densitometric Methods for Determination of Aceclofenac

ABSTRACTThree methods were developed for the determination of aceclofenac in the presence of its degradation product, diclofenac. In the first method, third-derivative spectrophotometry (D3) is used. The D3 absorbance is measured at 283 nm where its hydrolytic degradation product diclofenac does not interfere. The suggested method shows a linear relationship in the range of 4–24 µg mL−1 with mean percentage accuracy of 100.05±0.88. This method determines the intact drug in the presence of up to 70% degradation product with mean percentage recovery of 100.42±0.94. The second method depends on ratio-spectra first-derivative (RSD1) spectrophotometry at 252 nm for aceclofenac and at 248 nm for determination of degradation product over concentration ranges of 4–32 µg mL−1 for both aceclofenac and diclofenac with mean percentage accuracy of 99.81±0.84 and 100.19±0.72 for pure drugs and 100.17±0.94 and 99.73±0.74 for laboratory-prepared mixtures, respectively. The third method depends on the quantitative evaluation of thin-layer chromatography of aceclofenac using chloroform:methanol: ammonia (48:11.5:0.5 v/v/v) as a mobile phase. Chromatograms were scanned at 274 and 283 nm for aceclofenac and diclofenac, respectively. The method determined aceclofenac and diclofenac in concentration ranges of 2–10 and 1–9 µg spot−1 with mean percentage accuracy of 100.20±1.03 and 100.14±0.98 for pure drugs and 99.77±0.74 and 100.07±0.78 for laboratory-prepared mixtures, respectively. This method retains its accuracy in the presence of up to 80% degradation product for the studied drug.The suggested procedures were checked using laboratory-prepared mixtures and were successfully applied for the analysis of their pharmaceutical preparation. The validity of the proposed methods was further assessed by applying a standard addition technique. The obtained results agreed statistically with those obtained by the reported method.

Stability-Indicating Spectrophotometric and Densitometric Methods for Determination of Some Cephalosporins

abstract Two methods were developed for determination of intact ceftazidime (I), cefuroxime sodium (II), and cefotaxime sodium (III) in the presence of their degradation products. In the first method, first derivative spectrophotometry (D1) is used. The (D1) absorbance is measured at 268.6, 306, and 228.6 nm for I, II, and III, respectively. The first proposed method determines I, II, and III in concentration ranges of 5-50, 5-35, and 5-40 μg/mL, respectively, with corresponding mean accuracies of 99.7 ± 0.8, 100.1 ± 0.7, and 99.8 ± 0.8%. The method determines the intact drug in the presence of up to 90% degradation products for I, and II and up to 80% for III. The second method depends on the quantitative densitometric evaluation of thin-layer chromatograms of I, II, and III. It determines I, II, and III in concentration ranges of 4-16 μg for I and 2-12 μg for II and III, with mean accuracy's of 99.5 ± 0.8, 99.2 ± 0.7, and 99.7 ± 0.8% for I, II, and III, respectively. The second method retains its accuracy in the presence of up to 90% degradation products for the 3 drugs. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the official method.

The analytical consequence of the decomposition of prednisolone to 17-deoxyprednisolone in stability control

17-Deoxyprednisolone, a decomposition product of prednisolone, interferes in some stability-indicating spectrophotometric methods for corticosteroids. The false positive reaction of 17-deoxyprednisolone with tetrazolium blue and with the method ofBundgaard andHansen (1979), is discussed.