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Journal ArticleDOI: 10.1016/J.SAA.2020.119157

Simultaneous determination of elbasvir and grazoprevir in their pharmaceutical formulation by synchronous fluorescence spectroscopy coupled to dual wavelength method.

05 Mar 2021-Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (Elsevier)-Vol. 248, pp 119157-119157
Abstract: In the present study, a sensitive, selective and accurate synchronous fluorescence spectroscopic method was utilized for simultaneous estimation of elbasvir and grazoprevir in their pharmaceutical formulation. The developed method based on measurement of the synchronous fluorescence intensity of the studied drugs at constant wavelength difference (Δλ) = 50 nm. Elbasvir can be determined directly at 312 nm without interference from grazoprevir. Grazoprevir can be determined by application of dual wavelength method by taking the difference in synchronous fluorescence intensity at 390 & 372 nm to remove interference from elbasvir. Calibration graphs were found to be linear over the concentration range of 50–700 ng/mL for elbasvir and 100–900 ng/mL for grazoprevir. The developed method was successfully applied to the quantitative analysis of the two drugs in Zepatier® tablets.

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Topics: Elbasvir (65%), Grazoprevir (61%)
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5 results found


Journal ArticleDOI: 10.1016/J.SAA.2021.119505
Abstract: Artificial neural networks and genetic algorithm artificial neural networks, chemometric assisted spectrophotometric models, were developed for the quantitative analysis of elbasvir and grazoprevir in their newly FDA approved pharmaceutical dosage form. The UV absorption spectra of elbasvir and grazoprevir show severe degree of overlap which caused difficulty for selecting certain spectrophotometric method with advantage of simultaneous quantitative analysis of the cited drugs. After extensive study and many experimental trials, artificial neural networks and genetic algorithm artificial neural networks were the suitable models for the quantitative analysis of studied drugs in their binary mixture. Experimental design and constructing the calibration and validation sets of the binary mixture were achieved to implement the proposed models. The models were optimized with the aid of five-levels, two factors experimental design. The designed models were successfully applied to the quantitative analysis of Zepatier® tablets. The results were statistically compared with another reported HPLC quantitative analytical method with no significant difference by applying Student t-test and variance ratio F-test.

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Topics: Elbasvir (54%), Grazoprevir (52%)

3 Citations


Journal ArticleDOI: 10.1007/S42250-021-00253-9
18 Jun 2021-
Abstract: Elbasvir (ELB) and grazoprevir (GZP) were two new approved drugs and their co-formulation presents one of the more recently approved combinations for treatment of hepatitis C virus. A stability indicating reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous determination of ELB and GZP and their degradation products under hydrolysis and oxidative stress conditions as per International Conference on Harmonization [ICH Q1A (R2) guidelines]. Adequate chromatographic separation with well-defined peaks was achieved using a Waters Spherisorb phenyl Column (150 mm × 4.6 mm I.D, 5 µm particle size) with a temperature maintained at 40 °C ± 2 °C. The mobile phase consists of acetonitrile: 5 mM ammonium formate buffer (+ 0.1% v/v of trimethylamin, pH was adjusted to 3.2 by formic acid) (60:40 v/v) at a flow rate of 0.8 mL min−1. A validation study was performed according to the accuracy profile methodology. Specificity, suitability, robustness, precision and trueness of the developed method were confirmed. The proposed method was also successfully compatible to identification of molecular structure of degradation products by liquid chromatography-mass spectrometry (LC–MS) coupling. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization source was used to characterizing degradation products based on the MS spectra and accurate mass measurements.

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Topics: Elbasvir (53%)

Journal ArticleDOI: 10.1016/J.SAA.2021.120116
Abstract: Acetylsalicylic acid and omeprazole were recently formulated by the new FDA-approved drug Yosprala ® Tablets. This novel combination was prescribed to reduce the risk of myocardial infarction in patients who were at risk for developing peptic ulcer while taking acetylsalicylic acid. In the current work, two different high precision sensitive fluorescence spectroscopic methods were developed for quantitative analysis of the above drugs in pharmaceutical dosage form and spiked human plasma. Acetylsalicylic acid was quantitatively analyzed due to its unique native fluorescence nature. The fluorescence emission of acetylsalicylic acid was quantitatively determined at 404 nm after excitation at 296 nm without any interference from omeprazole. Omeprazole, which has a free terminal secondary amino group, reacted with 4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl) by a nucleophilic substitution mechanism to form a highly fluorescent dark yellow fluorophore. Omeprazole was quantitatively analyzed by measuring the emission fluorescence intensity of the dark yellow fluorophore at 535 nm after excitation at 465 nm. Various parameters affecting the described methods were carefully checked and optimized. The calibration curves were found to be linear over the concentration range of 50–1600 ng/ml for acetylsalicylic and 30–2000 ng/ml for omeprazole. The proposed methods were successfully applied to the quantitative analysis of the two drugs in the pharmaceutical dosage form Yosprala ® and in spiked human plasma.

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Topics: Dosage form (51%)

Journal ArticleDOI: 10.1080/10408347.2021.1923456
Abstract: Human beings are in dire need of developing an efficient treatment against fierce viruses like hepatitis C virus (HCV) and Coronavirus (COVID-19). These viruses have already caused the death of over two million people all over the world. Therefore, over the last years, many direct-acting antiviral drugs (DAADs) were developed targeting nonstructural proteins of these two viruses. Among these DAADs, several drugs were found more effective and safer than the others as sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir. The last one is indicated for COVID-19, while the rest are indicated for HCV treatment. Due to the valuable impact of these DAADs, larger number of analytical methods were required to meet the needs of the clinical studies. Therefore, this review will highlight the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites. These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period. Moreover, the analytical instrumentation and methods used in determination of these DAADs will be illustrated in tabulated forms.

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Topics: Glecaprevir (61%), Voxilaprevir (58%), Pibrentasvir (56%) ... show more

Journal ArticleDOI: 10.1016/J.SAA.2021.120235
Abstract: Curcumin is a natural product that is frequently utilized in cancer prevention and treatment. The significant benefit of vegetable-derived nutraceuticals in combination with widespread cytostatic medication such as ponatinib is to reduce toxicity and side effects. In this paper, we focus the study on analytical quantification of ponatinib and curcumin through highly sensitive synchronous spectrofluorometric method. Applying this method at Δλ = 160 nm, each of ponatinib and curcumin could be measured at 303 and 412 nm without interference from each others. The diverse experimental factors impacting the performance of the method were studied and optimized. The method exhibited a reasonable linearity in the ranges of 5.0–60.0 and 10.0–200.0 ng/mL for ponatinib and curcumin, respectively with detection limits of 1.48 and 1.22 ng/mL and quantitation limits of 4.49 and 3.68 ng/mL, respectively. The anticipated method was employed for the assessment and evaluation of the studied drugs in the spiked human plasma samples. The mean % recoveries in plasma samples (n = 6) for each of ponatinib and curcumin were 99.84 ± 1.86 and 100.06 ± 2.72, accordingly. The developed method was validated in conformity with the requirements of International Council of Harmonization (ICH).

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Topics: Ponatinib (56%)
References
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17 results found


Open accessBook
01 Apr 2005-
Abstract: 1 Introduction 11 Analytical problems 12 Errors in qunatitative analysis 13 Types of error 14 Random and systematic errors in titrimetric analysis 15 Handling systematic errors 16 Planning and design of experiments 17 Calculators and computers in statistical calculations 2 Statistics of Repeated Measurements 21 Mean and standard deviation 22 The distribution of repeated measurements 23 Log-normal distribution 24 Definition of a 'sample' 25 The sampling distribution of the mean 26 Confidence limits of the mean for large samples 27 Confidence limits of the mean for small samples 28 Presentation of results 29 Other uses of confidence limits 210 Confidence limits of the geometric mean for a log-normal distribution 211 Propagation of random errors 212 Propagation of systematic errors 3 Significance Tests 31 Introduction 32 Comparison of an experimental mean with a known value 33 Comparison of two experimental means 34 Paired t-test 35 One-sided and two-sided tests 36 F-test for the comparison of standard deviations 37 Outliers 38 Analysis of variance 39 Comparison of several means 310 The arithmetic of ANOVA calculations 311 The chi-squared test 312 Testing for normality of distribution 313 Conclusions from significance tests 314 Bayesian Statistics 4 The Quality of Analytical Measurements 41 Introduction 42 Sampling 43 Separation and estimation of variances using ANOVA 44 Sampling strategy 45 Quality control methods - Introduction 46 Stewhart charts for mean values 47 Stewhart charts for ranges 48 Establishing the process capability 49 Average run length: cusum charts 410 Zone control charts (J-charts) 411 Proficiency testing schemes 412 Method performance studies (collaborative trials) 413 Uncertainty 414 Acceptable sampling 415 Method validation 5 Calibration Methods in Instumental Analysis 51 Introduction: instrumentational analysis 52 Calibration graphs in instrumental analysis 53 The product-moment correlation coefficient 54 The line of regression of y on x 55 Errors in the slope and intercept of the regression line 56 Calculation of a concentration and its random error 57 Limits of detection 58 The method of standard additions 59 Use of regression lines for comparing analytical methods 510 Weighted regression lines 511 Intersection of two straight lines 512 ANOVA and regression calculations 513 Curvilinear regression methods - Introduction 514 Curve fitting 515 Outliers in regression 6 Non-parametric and Robust Methods 61 Introduction 62 The median: initial data analysis 63 The sign test 64 The Wald-Wolfowitz runs test 65 The Wilcoxon signed rank test 66 Simple tests for two independent samples 67 Non-parametric tests for more than two samples 68 Rank correlation 69 Non-parametric regression methods 610 Robust methods: introduction 611 Simple robust methods: trimming and winsorization 612 Further robust estimates of location and spread 613 Robust ANOVA 614 Robust regression methods 615 Re-sampling statistics 616 Conclusions 7 Experiimental Design and Optimization 71 Introduction 72 Randomization and blocking 73 Two-way ANOVA 74 Latin squares and other designs 75 Interactions 76 Identifying the important factors: factorial designs 77 Fractional factorial designs 78 Optimization: basic principles and univariate methods 79 Optimization using the alternating variable search method 710 The method of steepest ascent 711 Simplex optimization 712 Simulated annealing 8 Multivariate Analysis 81 Introduction 82 Initial analysis 83 Prinicipal component analysis 84 Cluster analysis 85 Discriminant analysis 86 K-nearest neighbour method 87 Disjoint class modelling 88 Regression methods 89 Multiple linear regression 810 Principal component regression 811 Partial least squares regression 812 Natural computation methods artificial neural networks 813 Conclusions Solutions to Exercises Appendix 1 Commonly used statistical significance tests Appendix 2 Statistical tables Index

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Topics: Robust regression (64%), Segmented regression (63%), Unit-weighted regression (63%) ... show more

3,666 Citations


Journal ArticleDOI: 10.1016/S0165-9936(02)01201-3
Digambara Patra1, Ashok Kumar Mishra1Institutions (1)
Abstract: The ability to analyse complex multi-component mixtures without resorting to tedious separation procedures is extremely useful for routine analysis. Single-wavelength fluorescence measurement is limited in its ability to analyse complicated multi-component samples when they have severely overlapping emission and/or excitation spectra. This can be overcome by using synchronous fluorescence scan (SFS), where overlapping of spectra can be minimized. The selectivity of SFS can still be increased by taking derivative spectrum, applying different multivariate methods, selective fluorescence quenching, three-dimensional synchronous measurement or using some of these procedures in combination. Recent developments in various synchronous fluorescence methods for analysis of multi-component systems are discussed in this review.

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261 Citations


Journal ArticleDOI: 10.1007/S10895-007-0238-5
Abstract: A rapid, simple and highly sensitive second derivative synchronous fluorometric method has been developed for the simultaneous analysis of binary mixture of cinnarizine (CN) and domperidone (DOM). The method is based upon measurement of the native fluorescence of these drugs at Δλ = 80 nm in aqueous methanol (50% V/V). The different experimental parameters affecting the native fluorescence of the studied drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.1 to 1.3 μg mL−1 and 0.1–3.0 μg mL−1 for CN and DOM, respectively with lower detection limits of 0.017 and 5.77 × 10−3 μg mL−1 and quantification limits of 0.058 and 0.02 μg mL−1 for CN and DOM. The proposed method was successfully applied for the determination of the studied compounds in synthetic mixtures and in commercial tablets. The results obtained were in good agreement with those obtained with reference methods. The high sensitivity attained by the synchronous fluorometric method allowed the determination of CN in real and spiked human plasma. The mean % recoveries in case of spiked human plasma (n = 3) were 96.39 ± 1.18 while that in real human plasma (n = 3) was 104.67 ± 4.16.

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42 Citations


Journal ArticleDOI: 10.1016/J.JPBA.2018.01.038
Abstract: Direct-acting antivirals (DAAs) represent a revolution in the treatment of chronic hepatitis C which have emerged at an extremely rapid pace over the past few years. DAAs act directly on the hepatitis C virus at various points in the viral life cycle to inhibit viral production. Among these novel DAAs, are daclatasvir (DCS) and ledipasvir (LDS). Herein, a novel, fast, simple, ultrasensitive and cost-effective spectrofluorimetric method was designed for determination of DCS and LDS in miscellaneous matrices. The method is based on investigation of the native fluorescence of the cited drugs. The relative fluorescence intensity (RFI) was measured at λex/λem equal to 315/381 nm for DCS and 332/387 nm for LDS. Under the optimum conditions, the linear ranges of calibration curves were 0.2–30 and 6–120 ng mL−1 for DCS and LDS, respectively with correlation coefficients ≥0.9998. The detection limits were 0.047 and 1.939 ng mL−1 for DCS and LDS, respectively indicating ultrasensitivity of the proposed method. Consequently, this permits in vitro and in vivo application of the proposed method in spiked and real human plasma with good percentage recovery (96.6–103.6%). The method was validated in compliance with ICH guidelines and US-FDA guidelines. Furthermore, the application was extended to analysis of DCS and LDS in its pharmaceutical formulations (either alone or in presence of other co-formulated drugs) and in synthetic mixture with sofosbuvir or ribavirin.

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Topics: Ledipasvir (53%), Daclatasvir (50%)

28 Citations


Journal ArticleDOI: 10.1016/J.SAA.2017.08.026
Abstract: The first three UV spectrophotometric methods have been developed of simultaneous determination of two new FDA approved drugs namely; elbasvir and grazoprevir in their combined pharmaceutical dosage form. These methods include simultaneous equation, partial least squares with and without variable selection procedure (genetic algorithm). For simultaneous equation method, the absorbance values at 369 (λmax of elbasvir) and 253nm (λmax of grazoprevir) have been selected for the formation of two simultaneous equations required for the mathematical processing and quantitative analysis of the studied drugs. Alternatively, the partial least squares with and without variable selection procedure (genetic algorithm) have been applied in the spectra analysis because the synchronous inclusion of many unreal wavelengths rather than by using a single or dual wavelength which greatly increases the precision and predictive ability of the methods. Successfully assay of the drugs in their pharmaceutical formulation has been done by the proposed methods. Statistically comparative analysis for the obtained results with the manufacturing methods has been performed. It is noteworthy to mention that there was no significant difference between the proposed methods and the manufacturing one with respect to the validation parameters.

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Topics: Elbasvir (57%), Grazoprevir (54%)

25 Citations


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