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BACKGROUND: Sulfasalazine and pentoxifylline are co-prescribed together to treat psoriasis and pemphigus vulgaris. Sulfasalazine is an anti-inflammatory, immunosuppressant, and antibiotic drug, while pentoxifylline is a vasodilator and immunosuppressant. The spectra of the two drugs and plasma suffer from severe overlap. OBJECTIVE: This work aims to simultaneously determine sulfasalazine and pentoxifylline in their binary mixture and spiked human plasma by the assessment of their UV spectral data. METHODS: Two model updated chemometric methods were established using principal component regression and partial least-squares regression models. The two models were validated in accordance with the U.S. Food and Drug Administration guidelines for bioanalysis and were applied for the determination of both drugs in synthetic mixtures or spiked human plasma. RESULTS: Accuracy and precision were within the accepted limits. In addition, three different assessment methods were used to evaluate the environmental greenness of the proposed models. CONCLUSION: The two updated models are simple, rapid, sensitive, and precise, and could be easily applied in QC laboratories for determination of sulfasalazine and pentoxifylline, without any preliminary separation steps or interference from plasma matrix. HIGHLIGHTS: Two updated chemometric models called principlal component regression and partial least-squares regression were established for determination of sulfasalazine and pentoxifylline in spiked human plasma using UV spectrophotometric data.
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Pentoxifilina , Humanos , Preparaciones Farmacéuticas , Sulfasalazina , Espectrofotometría/métodos , Análisis de los Mínimos Cuadrados , InmunosupresoresRESUMEN
Prednisolone (PDS) has recently been utilized to treat a variety of medical disorders, including autoimmune illnesses and cancer. It is also used to treat coronavirus disease 2019 infection-related respiratory problems. Because it may induce health problems including gastrointestinal lesions and ulceration, it has to be used alongside other drugs like esomeprazole (ESM), which acts as a proton pump antagonist to reduce the probability of ulceration. As a result, the goal of this research is to create an environmentally safe and sensitive high-performance liquid chromatography (HPLC) approach for determining PDS and ESM in their binary combination and spiked human plasma. C8 column (100 × 4.6 mm, 5 µm) and gradient mobile phase elution were used to separate the studied drugs with ultraviolet recognition at 290 nm. Caffeine was utilized as an internal standard to adjust the sample variance. Plasma, caffeine, ESM and PDS all had tR values of 1.4, 3.5, 6.3 and 7.3, respectively. The suggested method's greenness features were evaluated using three greenness evaluation tools: green analytical procedure index, analytical greenness metric approach and analytical eco-scale, and the findings were approved and satisfied. Validation parameters were evaluated in accordance with US-FDA recommendations in order to meet the global desires for biological analysis technique, acceptable limits were obtained.
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Recently, the main interest of analytical chemistry researchers has been the development of green analytical methods to minimize harmful effects on the environment and natural life. Therefore, an RP-HPLC method was developed and assessed regarding its greenness criteria using three greenness assessment tools: an analytical eco-scale, an analytical greenness metric approach and a green analytical procedure index. This method aims to separate and quantitatively determine three co-administered drugs, namely pyridostigmine bromide (PYR), 6-mercaptopurine (MRC) and prednisolone (PRD), in their tertiary mixture and spiked human plasma. These drugs are co-administered to manage myasthenia gravis autoimmune disease. The separation was done using a C18 column and a gradient elution of a mixture of 0.1% H3 PO4 aqueous solution (pH 2.3) and methanol. The flow rate was adjusted to 1 ml/min and detection was done at 254 (for PYR and PRD) and at 330 nm (for MRC). The lower limits of quantitation were 15, 2, and 5 µg/ml for PYR, MER and PRD, respectively. Linear correlations were obtained and found to be near 1. In addition, the proposed method was validated according to the US Food and Drug Administration's instructions, and the results proved its success to determine the three studied drugs in their tertiary mixture and spiked human plasma.
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Cromatografía , Miastenia Gravis , Estados Unidos , Humanos , Miastenia Gravis/tratamiento farmacológico , Cromatografía Líquida de Alta Presión/métodosRESUMEN
BACKGROUND: Prednisolone, 6-mercaptopurine, and pyridostigmine bromide are co-administered together to treat a neuromuscular autoimmune disease called myasthenia gravis. Prednisolone and 6-mercaptopurine are immunosuppressant drugs. 6-Mercaptopurine is the active form of the pro-drug azathioprine. Pyridostigmine bromide is a cholinesterase enzyme inhibitor. Curently, green characteristics are taken into account by analysts when they develop new methods. OBJECTIVE: The spectra of the three compounds and plasma are highly overlapped, so this study aims to remove this overlap and determine the three components quantitatively in raw powders and spiked human plasma using green methods. METHODS: Two multivariate updated chemometric models called principle component analysis and partial least-squares were developed. Three greenness assessment tools: the eco-scale, the analytical greenness metric approach, and the green analytical method index, were used to evaluate the greenness behavior of the generated models. RESULTS: The two models were verified in accordance with Food and Drug Administration requirements, and the results were within acceptable limits. In addition they are relatively green in accordance with the abovementioned greenness evaluation tools. CONCLUSION: The developed models succeeded in determining the proposed drugs in their tertiary combinations and spiked human plasma with satisfactory precision, accuracy, and good greenness behavior. HIGHLIGHTS: Two ecologically evaluated, multivariate spectrophotometric methods were developed for the determination of pyridostigmine bromide, 6-mercaptopurine, and prednisolone in spiked human plasma.
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Miastenia Gravis , Bromuro de Piridostigmina , Estados Unidos , Humanos , Bromuro de Piridostigmina/análisis , Bromuro de Piridostigmina/uso terapéutico , Mercaptopurina , Quimiometría , Miastenia Gravis/tratamiento farmacológico , PrednisolonaRESUMEN
Fluphenazine HCl (FLU) is an anxiolytic, while Nortriptyline HCl (NOR) is an anti-depressant. They are co-formulated together to treat depression and schizophrenia. Perphenazine (PER) and dibenzosuberone (DBZ) are the pharmacopeial impurities of FLU and NOR, respectively. Four spectrophotometric and multivariate chemometric methods were developed to determine the two drugs together or in presence of their two impurities in their bulk and pharmaceutical formulation. Method (A) is the triple divisor-ratio derivative (TDR) method, where the zero order spectrum of each component was divided by a mixture of the other 3 components, then the peak amplitudes of the first derivative spectra of FLU, NOR and DBZ were measured at 265, 245.4 and 283.2 nm, respectively. Method (B) is the double divisor-ratio difference-dual wavelength (DD-RD-DW) method, in which each component spectrum mixture was divided by a binary mixture of 2 of the interfering components. In the resulting ratio spectra, the amplitude difference is calculated between 2 wavelengths at which the third interfering component has zero difference. Methods (C and D) are the principle component analysis (PCA) and partial least squares (PLS) models. Methods (A and B) failed to quantify PER (FLU impurity), while (C and D) succeeded to quantify all components. The four methods have been applied for the prediction of the FLU and NOR in their pharmaceutical formulation with good accuracy and precision. The proposed methods have been validated according to the ICH guidelines and the results were within the acceptable limits.
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Nortriptilina , Perfenazina , Dibenzocicloheptenos , Composición de Medicamentos , Flufenazina , Espectrofotometría/métodosRESUMEN
Recently, prednisolone has been used in treating many medical conditions, such as autoimmune diseases and cancer. It is also prescribed to mitigate the respiratory complications caused by COVID-19 infection. It can cause some health complications, such as GIT ulcers, so it should be co-administered with proton-pump inhibitors, such as esomeprazole, to prevent the risk of ulcers. This work aims to develop an ecofriendly and sensitive TLC method for simultaneous determination of esomeprazole and prednisolone in their binary mixtures and spiked human plasma. Separation was performed using a mixture of ethyl acetate, methanol, and ammonia (9.5:0.5:0.1, v/v/v) as an eluting system with UV scanning at 245 nm. Dapoxetine was used as an internal standard to correct the variation during sampling. The resulting Rf values for plasma, esomeprazole, prednisolone, and dapoxetine were 0.03, 0.51, 0.72 and 0.85, respectively. Four greenness assessment tools-national environmental method index, eco-scale assessments, analytical greenness metric approach (AGREE), and green analytical procedure index (GAPI)-were used to evaluate the greenness characteristics of the proposed method to the environment, and the results were acceptable and satisfactory. Validation parameters were checked according to the US FDA guidelines to achieve the international requirements for bioanalytical method validation, and the results were within the accepted ranges.
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COVID-19 , Esomeprazol , Cromatografía en Capa Delgada/métodos , Humanos , Prednisolona , Reproducibilidad de los Resultados , ÚlceraRESUMEN
A validated RP-HPLC method was developed for the estimation of paracetamol, caffeine, metoclopramide and ergotamine simultaneously in bulk and pharmaceutical formulation. The method was extended for the determination of two paracetamol genotoxic and nephrotoxic impurities and degradation products namely p-aminophenol and 4-chloroacetanilide. Separation was done on octadecyl column (15 cm × 2.1 mm, 5 µm). Gradient elution was performed using mobile phase consisting of acetonitrile and water (pH 3) in ratio of (20: 80, v/v) for the first 3 min, (50: 50, v/v) for the next 4.5 min, then (20: 80, v/v) for the final 2.5 min. The flow rate was 0.7 mL/min throughout the run which took 10 min. UV detection was done at 230 nm. The proposed method agreed with ICH guidelines of method validation. The suggested method was applied for the estimation of the proposed drugs in their dosage form. Statistical comparison was done between the results obtained from the suggested method and those obtained from reported HPLC method. The proposed method is more beneficial than the published one because of having higher sensitivity and selectivity as it allows the detection of the proposed drugs in lower concentrations in the presence of paracetamol toxic impurities, p-aminophenol and 4-chloroacetanilide.
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Acetaminofén , Aminofenoles , Acetanilidas , Aminofenoles/análisis , Cromatografía Líquida de Alta Presión/métodosRESUMEN
BACKGROUND: Prednisolone (PRD) is an immunosuppressant and anti-inflammatory drug, although it may cause peptic ulcers as a side effect. Esomeprazole (ESO) is used for the treatment of peptic ulcers, therefore the two drugs are co-administered in cases of organ transplantation and autoimmune diseases. OBJECTIVE: This work aims to determine the two drugs simultaneously, in bulk, and in spiked human plasma by eliminating the overlap of their spectra and the interference of the plasma matrix. METHODS: Two simple and effective updated chemometric models-principal component analysis (PCA) and partial least squares (PLS)-were established using UV spectrophotometric data. RESULTS: The two updated models have been validated according to the U.S. Food and Drug Administration guidelines with acceptable results. The results were statistically compared with those of the reported methods, where no significant difference was found, indicating the validity of the developed methods. The two updated models have been successfully applied for prediction of the proposed drugs with good accuracy and precision. CONCLUSION: The two updated models are simple, rapid, sensitive, and precise and could be easily applied in quality control laboratories for determination of PRD and ESO, without any preliminary separation steps or interference from plasma matrixes. HIGHLIGHTS: Two model updated chemometric models, PCA and PLS, were established for determination of PRD and ESO in spiked human plasma using UV spectrophotometric data.
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Esomeprazol , Preparaciones Farmacéuticas , Quimiometría , Humanos , Análisis de los Mínimos Cuadrados , Prednisolona , EspectrofotometríaRESUMEN
BACKGROUND: Duloxetine hydrochloride (DUL) is a drug used to treat depression and anxiety. 1-Naphthol is a potential toxic impurity of DUL, as it causes hepatotoxicity in humans, and it is harmful to aquatic life. OBJECTIVE: Three simple, selective, rapid, accurate and precise methods were developed and validated according to International Conference on Harmonization (ICH) guidelines with respect to linearity, accuracy, precision and selectivity for analysis of duloxetine hydrochloride (DUL) in the presence of its potential toxic impurity 1-Naphthol in different laboratory-prepared mixtures and pharmaceutical formulations. METHODS: Method (A) is the first derivative of the ratio spectra spectrophotometric (1DD) method which allows determination of DUL at 251 nm and 1-Naphthol at 305.2 nm without interference from each other. Method B (dual wavelength) means that two different wavelengths were chosen to each drug, where the absorbance difference at these two wavelengths is equal to zero to the second drug. The chosen two wavelengths for DUL were 221.4 nm and 235.6, where the absorbance difference for 1-naphthol at these two wavelengths was equal to zero. While the chosen wavelengths for 1-naphthol were 247.8 nm and 297 nm, where the absorbance difference for DUL at these two wavelengths was equal to zero. Method (C) is the mean centering of ratio spectra spectrophotometric (MCR) method, which depends on measuring the mean centered values of ratio spectra of both DUL and 1-Naphthol at 226 nm. RESULTS: These methods were validated and agreed with the requirements of ICH guidelines with respect to linearity, accuracy, precision and selectivity. CONCLUSIONS: The results indicate the ability of developed methods to be used for routine quality control analysis of DUL in bulk and pharmaceutical formulations in the presence of its potential impurity 1-Naphthol.
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Naftoles , Clorhidrato de Duloxetina , Humanos , EspectrofotometríaRESUMEN
A novel ecofriendly, cost and time saving high-performance thin-layer chromatographic method was developed and validated for simultaneous determination of metoclopramide, ergotamine, caffeine, and paracetamol in bulk and pharmaceutical formulation. The separation was carried out on silica gel plates, using ethyl acetate:ethanol:ammonia (9:1:0.1, v/v/v) as a developing system. Ultraviolet detection was carried out at 272 nm. The resulting retention times were 0.15, 0.36, 0.49, and 0.74 min for metoclopramide, ergotamine, caffeine, and paracetamol, respectively. The greenness profile assessment was achieved to the proposed method to evaluate its greenness characters to the environment with acceptable results. Validation parameters were checked according to International Conference of Harmonization guidelines to achieve the international requirements for quality control analysis of the proposed drugs.
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Acetaminofén/análisis , Cafeína/análisis , Ergotamina/análisis , Metoclopramida/análisis , Cromatografía en Capa Delgada , Composición de Medicamentos , Estructura MolecularRESUMEN
Dapoxetine hydrochloride (DAP) and Tadalafil (TAD) were separated and determined quantitatively using a validated green high-performance thin layer chromatographic (HPTLC) method in their binary mixtures either as raw materials or in pharmaceutical formulations. The concentration ranges were 0.1-1.6 and 0.2-2.5 µg/band for dapoxetine and tadalafil, respectively, with accuracies of 98.93% ± 0.62 and 99.26% ± 1.39, respectively. Silica gel HPTLC F254 plates were used to carry out the separation. The mobile phase used was a mixture of ethanol-ethyl acetate (1:9 by volume), which is environmentally green and harmless. Densitometric scanning with UV detector was used to detect the separated peaks at 222 nm. ICH guidelines were followed to validate the suggested method, and the results prove that they can be used for regular analysis in quality control laboratories with compatible results.
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Bencilaminas/análisis , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Naftalenos/análisis , Tadalafilo/análisis , Acetatos/química , Calibración , Combinación de Medicamentos , Etanol/química , Reproducibilidad de los Resultados , Comprimidos/análisisRESUMEN
BACKGROUND: Dapoxetine (DAP) is a serotonin-norepinephrine reuptake inhibitor, and Tadalafil (TAD) is a phosphodiesterase type-5 inhibitor. Both are coformulated as tablets called Erectafil® for treatment of erectile ejaculation. OBJECTIVE: DAP and TAD were analyzed in their binary mixtures and pharmaceutical formulations using two multivariate calibration chemometric models. METHODS: Partial least-squares (PLS) and linear support vector regression (SVR) models were applied using two factor-four level experimental design and UV-spectrophotometric data. They were compared to each other, and their advantages and disadvantages were discussed. RESULTS: The developed methods succeeded to determine DAP and TAD in different ratios with good results regarding International Conference on Harmonization guidelines. Linearity ranges were 2-15 µg/mL and 3-30 µg/mL for DAP and TAD, respectively, with good accuracy of 100 ± 0.37 for DAP and 100 ± 0.8 for TAD regarding PLS model and 100.04 ± 0.32 for DAP and 99.89 ± 0.77 for TAD regarding SVR model. Good precision values of 0.787 for DAP and 0.793 for TAD regarding PLS model and 1.105 for DAP and 0.930 for TAD regarding SVR model were obtained. The two models were applied on the dosage forms and statistically compared with the published HPLC method with no significant difference regarding accuracy and precision. CONCLUSIONS: The two models can be utilized for routine analysis and QC of DAP and TAD in their bulk and pharmaceutical formulations. The SVR model gives better results and generalization ability than those of the PLS model regarding accuracy and prediction error, while the latter is better for being simpler and faster.
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Bencilaminas , Calibración , Análisis de los Mínimos Cuadrados , Naftalenos , Comprimidos , TadalafiloRESUMEN
Three rapid, simple and selective spectrophotometric methods were developed for determination of Dapoxetine Hydrochloride (DAP) and Tadalafil (TAD) in bulk and pharmaceutical dosage forms. Method (A) is simultaneous first derivative (1D) spectrophotometric method in which the peak amplitudes of the first derivative spectra (1D) were measured for both DAP and TAD at 322.4â¯nm and 230â¯nm, respectively with no interference from each other. Method (B) is the area under curve (AUC) spectrophotometric method in which the areas under curve in the wavelength ranges 228-240â¯nm and 242-254â¯nm are used for determination of DAP and TAD respectively. Method (C) is ratio subtraction combined with extended ratio subtraction spectrophotometry (EXRS) in which TAD was determined by dividing the mixture spectra by the spectrum of 15⯵g/mL solution of DAP, while DAP was be determined by dividing the mixture spectra by the spectrum of 30⯵g/mL solution of TAD. The developed methods were applied to different laboratory prepared mixtures of DAP and TAD. These methods were validated according to the ICH guidelines with respect to linearity, accuracy, precision, selectivity and specificity, and can be used for routine quality control analysis of DAP and TAD in their dosage forms.