Stability indicating eco-friendly quantitation of terbutaline and its pro-drug bambuterol using quantitative proton nuclear magnetic spectroscopy.

Quantitative 1H-NMR became an increasingly important issue in pharmaceutical analytical chemistry. This study used NMR spectroscopy to assay the bronchodilator drug terbutaline sulfate and its pro-drug bambuterol hydrochloride in pure form and pharmaceutical preparations. The technique proceeded using deuterium oxide (D2O) as an 1H-NMR solvent and phloroglucinol anhydrous as an internal standard (IS). Comparatively, to the phloroglucinol signal at 5.9 ppm, the resulting quantitative signals of the studied drugs were corrected. The terbutaline singlet signal at 6.3 ppm was chosen for quantification, while the bambuterol quantitative singlet signal was at 2.9 ppm. The two drugs were rectilinear over the concentration range of 1.0-16.0 mg/mL. LOD values were 0.19 and 0.21 mg/mL while LOQ values were 0.58 and 0.64 mg/mL for terbutaline and bambuterol respectively. The developed method has been validated according to the International Conference of Harmonization (ICH) regarding linearity, accuracy, precision, specificity, and robustness. A greenness profile assessment was applied, and the method proved to be green. The method enables the assay of the two drugs in pure drug and pharmaceutical preparations. The method also enables the assay of the two drugs in the presence of each other; thus, it is considered a stability-indicating method where terbutaline is an acid degradation product of bambuterol.

Red cell distribution width, neutrophil lymphocyte ratio and interleukin 10 are good prognostic markers in multiple myeloma.

Background: Multiple myeloma (MM) is still an incurable disease so we need to continue developing new diagnostic and prognostic options for its management. There are multiple prognostic factors for MM, but most of them are costly and time consuming. Hence comes the urge to identify bed side and low cost prognostic tools, that is why this study was aiming to identify in Egyptian MM patients. Materials and methods: The study was carried on 60 newly diagnosed multiple myeloma patients and 20 age and sex matched healthy individuals as controls. Studied subjects were subdivided into two groups: Group I: 60 multiple myeloma patients which were subdivided into three subgroups: Stage I: 10 patients, Stage II: 17 patients, Stage III: 33 patients, Group II: 20 healthy controls. Results: A progressive significant increase in IL-10, RDW, NLR, and beta2 microglobulin (ß2M) with disease progression from stage I towards stage III as compared to the control group. However, IL-10, RDW, and NLR have the best prognostic efficiency value regarding to sensitivity, specificity and positive predictive value when compared with ß2M. Conclusions: IL-10, RDW, and NLR are simple, easy and bedside tests (in the case of RDW, and NLR). They have high sensitivity and specificity when compared to ß2M, which is a well-established prognostic factor that highlights the valuable role they play as prognostic markers in MM.

Utility and greenness appraisal of nuclear magnetic resonance for sustainable simultaneous determination of three 1,4-benzodiazepines and their main impurity 2-amino-5-chlorobenzophenone.

A robust, stability-indicating, and eco-friendly proton nuclear magnetic resonance (1H-qNMR) method was developed for the concurrent determination of three 1,4-benzodiazepines (BDZs), namely diazepam (DZP), alprazolam (ALP), and chlordiazepoxide (CDP) and their common impurity, synthesis precursor, and degradation product; 2-amino-5-chlorobenzophenone (ACB). In the present method, a novel approach was developed for composing a green and cost-efficient solvent system as an alternative to the common NMR organic solvents utilizing 0.3 M sodium dodecyl sulfate prepared in deuterated water. The conducted method is characterized by simplicity with no need for sample pretreatment or labeling. Phloroglucinol was used as an internal standard. The chosen signals for the determinations of ALP, CDP, DZP and ACB were at 2.35 ppm (singlet), 2.84 ppm (singlet), 3.11 ppm (singlet), and 6.90 ppm (doublet of doublet), respectively. The proposed method possessed linearity over the concentration range of 0.25-15.0 mg ml-1 for DZP, ALP, CDP and of 0.5-25.0 mg ml-1 for ACB with LOD values of 0.06, 0.03, 0.07 and 0.16 mg ml-1 respectively, and LOQ values of 0.18, 0.09, 0.21 and 0.49 mg ml-1, respectively. Accuracy of the method was evidenced by excellent recovery% (99.57-99.90%) and small standard deviation (≥ 1.10) for the three analyzed drugs. Intra- and inter-day precision were determined with coefficient of variation ranging from 0.12 to 1.14 and from 0.72 to 1.67, respectively. For the studied compounds, appraisal of the method greenness was achieved via four approaches: Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), Analytical greenness metric (AGREE), and RGB Additive Color Model. The results proved that the proposed method has the privilege of being a green analytical method.

Comparative Assessment of SSR and RAPD markers for genetic diversity in some Mango cultivars.

Genetic improvement mainly depends on the level of genetic variability present in the population, and the degree of genetic diversity in a population largely determines the rate of genetic advancement. For analyzing genetic diversity and determining cultivar identities, a molecular marker is a useful tool. Using 30 SSR (simple sequence repeat) and 30 RAPD (randomly amplified polymorphic DNA) markers, this study evaluated the genetic divergence of 17 mango cultivars. The effectiveness of the two marker systems was evaluated using their genetic diversity characteristics. Additionally, the effects of SM (simple matching) and Dice similarity coefficients and their effects on mango clustering were evaluated. The findings showed that SSR markers generated 192 alleles, all of which were polymorphic (100%). With RAPD markers, 434 bands were obtained, 361 of which were polymorphic (83%). The average polymorphic information content (PIC) for RAPD and SSR was 0.378 and 0.735, respectively. Using SSR markers resulted in much higher values for other genetic diversity parameters compared to RAPD markers. Furthermore, grouping the genotypes according to the two similarity coefficients without detailed consideration of these coefficients could not influence the study results. The RAPD markers OPA_01, OPM_12 followed by OPO_12 and SSR markers MIAC_4, MIAC_5 followed by mMiCIR_21 were the most informative in terms of describing genetic variability among the cultivars under study; they can be used in further investigations such as genetic mapping or marker-assisted selection. Overall, 'Zebda' cultivar was the most diverse of the studied cultivars.

Validated spectrofluorimetric assay of two co-administered drug mixtures containing hydroxychloroquine with either moxifloxacin or ofloxacin as a drug regimen for hospital-acquired pneumonia in patients with COVID-19.

Moxifloxacin and ofloxacin are two broad-spectrum quinolone antibiotics. They are among the most widely used antibiotics, at this time, applied to control the COVID-19 pandemic. Hydroxychloroquine is an FDA-approved drug for the treatment of COVID-19. This work describes a simple, green, selective, and sensitive spectrofluorimetric method for the assay of moxifloxacin and ofloxacin in the presence of hydroxychloroquine, two co-administered mixtures used in the treatment of hospital-acquired pneumonia in patients with COVID-19. Simultaneous assay of hydroxychloroquine and moxifloxacin was carried out in methanol using a direct spectrofluorimetric method (method I) at 375 and 550 nm, respectively, after excitation at 300 nm. The direct spectrofluorimetric assay was rectilinear over concentration ranges 50.0-400.0 and 300.0-2500.0 ng/ml for hydroxychloroquine and moxifloxacin, respectively, with limits of detection (LOD) of 6.4 and 33.64 ng/ml and limits of quantitation (LOQ) of 19.4 and 102.6 ng/ml, respectively, for the two drugs. The assay for hydroxychloroquine and ofloxacin was carried out by measuring the first derivative synchronous amplitude for hydroxychloroquine at the zero crossing point of ofloxacin and vice versa at Δλ = 140 nm (method II). Hydroxychloroquine was measured at 266 nm, while ofloxacin was measured at 340 nm over the concentration range 4-40 ng/ml for hydroxychloroquine and 200-2000 ng/ml for ofloxacin with LOD of 0.467 and 25.3 ng/ml and LOQ of 1.42 and 76.6 ng/ml, respectively, for the two drugs. The two methods were validated following International Conference on Harmonization guidelines and were applied to the analysis of the two drugs in plasma with good percentage recoveries (109.73-93.17%).

Fast one-pot microwave-assisted green synthesis of highly fluorescent plant-inspired S,N-self-doped carbon quantum dots as a sensitive probe for the antiviral drug nitazoxanide and hemoglobin.

In this study, we report a one-pot, green, cost-efficient, and fast synthesis of plant-based sulfur and nitrogen self-co-doped carbon quantum dots (S,N-CQDs). By 4-min microwave treatment of onion and cabbage juices as renewable, cheap, and green carbon sources and self-passivation agents, blue emissive S,N-CQDs have been synthesized (λex/λem of 340/418 nm) with a fluorescence quantum yield of 15.2%. A full characterization of the natural biomass-derived quantum dots proved the self-doping with nitrogen and sulfur. The S,N-CQDs showed high efficiency as a fluorescence probe for sensitive determination of nitazoxanide (NTZ), that recently found wide applicability as a repurposed drug for COVID-19, over the concentration range of 0.25-50.0 µM with LOD of 0.07 µM. The nanoprobe has been successfully applied for NTZ determination in pharmaceutical samples with excellent % recovery of 98.14 ± 0.42. Furthermore, the S,N-CQDs proved excellent performance as a sensitive fluorescence nanoprobe for determination of hemoglobin (Hb) over the concentration range of 36.3-907.5 nM with a minimum detectability of 10.30 nM. The probe has been applied for the determination of Hb in blood samples showing excellent agreement with the results documented by a medical laboratory. The greenness of the developed probe has been positively investigated by different greenness metrics and software. The green character of the proposed analytical methods originates from the synthesis of S,N-CQDs from sustainable, widely available, and cheap plants via low energy/low cost microwave-assisted technique. Omission of organic solvents and harsh chemicals beside dependence on mix-and-read analytical approach corroborate the method greenness. The obtained results demonstrated the substantial potential of the synthesized green, safe, cheap, and sustainable S,N-CQDs for pharmaceutical and biological applications.

Eco-friendly spectrophotometric methods for determination of remdesivir and favipiravir; the recently approved antivirals for COVID-19 treatment.

Remdesivir (REM) and Favipiravir (FAV) are recently approved antivirals prescribed in severely ill COVID-19 patients. Therefore, development of new, simple, rapid, sensitive, and selective methods for analysis of such drugs in their pharmaceutical formulations will be highly advantageous. Herein, we have developed different spectrophotometric methods for analysis of the studied analytes. Method I is based on direct spectrophotometric analysis of REM and FAV in ethanol at λmax 244 and 323 nm, respectively. For simultaneous quantitation of REM and FAV, methods II-V were followed. Method II is based on derivative spectrophotometry in which REM was determined in second-order derivative spectra at 248 nm (the zero-crossing wavelength for FAV), while FAV was measured in first-order derivative spectra at 337 nm (the zero-crossing point for REM). Method III is the dual-wavelength method in which spectral intensities were subtracted at 244-207 nm for REM and at 330-400 nm for FAV. Method IV is the ratio subtraction in which ratio spectra were obtained by a suitable divisor followed by subtraction of intensities at 272-340 nm and 335-222 nm for REM and FAV, respectively. Method V is the derivative ratio method in which the obtained ratio spectra in method IV were converted to first-order derivative and then REM and FAV were recorded at 280 and 340 nm, respectively. Calibration graphs were linear in the ranges of 1-10 µg/mL for REM through all methods and 1-20 µg/mL for FAV in methods I and II, and 2-20 µg/mL by the other methods. The evolved methods were applied to pharmaceutical dosage forms of REM and FAV. All the proposed methods were further applied to human plasma samples containing both drugs with acceptable mean recoveries.

Conventional and synchronous spectrofluorometric determination of the recently administered drugs for treatment of COVID-19 favipiravir and apixaban.

COVID-19 is a fast-spreading pandemic that is caused by SARS-CoV-2 viral pathogen. Combination therapy of the antiviral favipiravir and the anticoagulant apixaban is one of the efficient treatment regimens. Therefore, development of novel and sensitive methods for simultaneous analysis of such combination is highly advantageous. Herein, two eco-friendly, simple, rapid, and cost-effective spectrofluorometric methods were evolved for the estimation of favipiravir and apixaban in pharmaceutical and biological matrices. Method I was based on analysis of favipiravir and apixaban by the first-order derivative of the conventional fluorescence spectra obtained after excitation at 300 nm, where favipiravir and apixaban were detected at 468.8 and 432.0 nm, respectively. Method II relied on dual scan synchronous spectrofluorometry, in which favipiravir was determined at 364 nm using Δλ = 60 nm while apixaban was analyzed at 274 nm using Δλ = 200 nm. Method optimization was performed for selecting the optimum conditions at which maximum sensitivity and selectivity were obtained. This report is the first one that describes simultaneous analysis of favipiravir and apixaban by synchronous spectrofluorometry. The developed methods were successfully applied to evaluate favipiravir and apixaban in spiked human plasma and in pharmaceutical dosages with high %recoveries and low RSD.

A synchronous spectrofluorometric technique for simultaneous detection of alfuzosin and tadalafil: applied to tablets and spiked biological samples.

A facile, accurate, eco-friendly and sensitive spectrofluorometric method was evolved to assay alfuzosin hydrochloride (AFH) and tadalafil (TDF) in different matrices. Such a co-administered combination is clinically used for the treatment of lower urinary tract symptoms. Both compounds are characterized by their native fluorescence spectra upon excitation at specific wavelengths. Their characteristic fluorescence spectra were used for sensitive assay of the studied analytes in tablets and human biological samples. The assay principle is based on first-order synchronous spectrofluorometric scan using Δλ = 60 nm in which AFH peaks were recorded at 366 nm. Meanwhile, TDF measurements were recorded at 293 nm in the same scans without overlap with AFH spectra. Recent analytical chemistry trends were implemented to lessen occupational and environmental perils, using ethanol as a diluting solvent for method optimization and application. Linearity ranges were 5.0-90.0 and 10.0-100.0 ng ml-1 for AFH and TDF, respectively in their raw materials with average % recoveries of 100.44% and 99.73% in raw materials, 100.15% and 100.20% in spiked plasma, and 97.14% and 99.99% in spiked urine. The proposed method was successfully applied to Prostetrol and Starkoprex commercial tablets with no interference with common tablet additives.

Development of three ecological spectroscopic methods for analysis of betrixaban either alone or in mixture with lercanidipine: greenness assessment.

Three eco-friendly spectrophotometric methods were developed for determination of the novel anticoagulant drug, betrixaban (BTX). The first method (method A) was based on direct analysis of BTX at 229.4 nm on the zero-order spectrum using methanol as the optimum solvent. While the second method (method B) was based on measuring difference absorption value (ΔA) of BTX at 335 nm, which was obtained from pH-induced spectral difference (difference spectra of BTX in 0.1 M NaOH versus 0.1 M HCl). The third method (method C) was based on measurement of the first-derivative amplitudes of BTX and its co-administered Ca channel blocker lercanidipine (LER) at 304 and 229 nm for simultaneous assay of BTX and LER, respectively. All methods were linear over concentration ranges of 1.0-20.0 and 8.0-80.0 µg ml-1 for BTX in methods A and B, respectively, and of 1.0-20.0 and 1.0-25.0 µg ml-1 for BTX and LER, respectively, in method C. The three methods were fully validated and assessed for greenness by three metrics: analytical eco-scale, green analytical procedure index and Analytical GREEnness metrics. The results indicated the validity and greenness of the proposed methods. Moreover, the methods were applied to assay the studied analytes in their dosage forms with high percentage of recovery and low percentage of relative s.d. values.

Utilization of a micellar matrix for simultaneous spectrofluorimetric estimation of alfuzosin hydrochloride and vardenafil hydrochloride.

A sensitive and direct spectrofluorimetric method was developed for simultaneous quantitation of two co-administered drugs, namely, alfuzosin hydrochloride (AFH) and vardenafil hydrochloride (VRH). Both drugs exhibited native fluorescence properties that could be exploited to assay them in biological fluids with high sensitivity. Spectrofluorimetric analysis of AFH and VRH is based on excitation of both drugs at 265 nm where emission spectra were recorded separately for AFH and VRH at 380 and 485 nm, respectively. Micellar trends in analytical chemistry were adopted to minimize both environmental and occupational hazards, using distilled water and sodium dodecyl sulphate (serves as a micellar medium that enhanced the sensitivity of AFH and VRH) for analysis of both drugs in their raw materials, tablets, and human biological fluids (plasma and urine). Linearity ranges were 1.0-16.0 and 10.0-700.0 ng mL-1 for AFH and VRH, respectively. The proposed method was successfully assessed for analysis of AFH and VRH in spiked human plasma and urine samples over the following concentrations: 1.0-12.0 ng mL-1 and 4.0-400.0 ng mL-1 for both drugs, simultaneously with mean recoveries of 101.08 % and 102.06 % in plasma and 96.75 % and 92.8 % in urine. Statistical analysis of the practical results has proved quite good agreement and revealed there were no significant differences in the accuracy and precision with those obtained by the comparison methods. The proposed method was applied successfully to Prostetrol® and Powerecta® commercial tablets without interference with tablet additives.

MiR-150 Expression in Chronic Myeloid Leukemia: Relation to Imatinib Response.

OBJECTIVE: To assess the circulating micro-RNA-150 (miR-150) expression in patients with chronic myeloid leukemia (CML) in relation to imatinib response. METHODS: Sixty patients with CML and 20 age- and sex-matched control subjects were enrolled. Circulating miR-150 levels were assessed by quantitative real-time polymerase chain reaction on days 0, 14, and 90 of imatinib therapy for patients and once for control subjects. RESULTS: The baseline miR-150 expression was significantly lower in patients with CML than in control subjects with subsequent elevation at 14 and 90 days after the start of imatinib treatment. Early treatment response (ETR) at 90 days was the main study outcome. The miR-150 expression had a significantly higher level in patients with CML with ETR. On multivariate analysis, miR-150 on day 14 was significantly related to ETR in patients with CML with predictive efficacy (area under the curve = 0.838, 72.9% sensitivity, and 84.2% specificity). CONCLUSION: We found that miR-150 expression on day 14 of imatinib treatment is a useful early predictive candidate for imatinib response in patients with CML.

Quantitative proton nuclear magnetic resonance method for simultaneous analysis of fluticasone propionate and azelastine hydrochloride in nasal spray formulation.

A facile, rapid, accurate and selective quantitative proton nuclear magnetic resonance (1H-qNMR) method was developed for the simultaneous determination of fluticasone propionate (FLP) and azelastine hydrochloride (AZH) in pharmaceutical nasal spray for the first time. The 1H-qNMR analysis of the studied analytes was performed using inositol as the internal standard and dimethyl sulfoxide-d6 (DMSO-d6) as the solvent. The quantitative selective proton signal of FLP was doublet of doublet at 6.290, 6.294, 6.316 and 6.319 ppm, while that of AZH was doublet at 8.292 and 8.310 ppm. The internal standard (inositol) produced a doublet signal at 3.70 and 3.71 ppm. The method was rectilinear over the concentration ranges of 0.25-20.0 and 0.2-15.0 mg ml-1 for FLP and AZH, respectively. No labelling or pretreatment steps were required for NMR analysis of the studied analytes. The proposed 1H-qNMR method was validated efficiently according to the International Council on Harmonisation guidelines in terms of linearity, limit of detection, limit of quantification, accuracy, precision, specificity and stability. Moreover, the method was applied to assay the analytes in their combined nasal spray formulation. The results ensured the linearity (r 2 > 0.999), precision (% RSD < 1.5), stability, specificity and selectivity of the developed method.

Optimization and Validation of a Facile RP-HPLC Method for Determination of Betrixaban and Lercanidipine in Pharmaceutical and Biological Matrices.

A simple, accurate, rapid and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method was established for determination of a novel non-vitamin K antagonist oral anticoagulant drug, betrixaban, and its co-administered calcium-channel blocker drug, lercanidipine, in pharmaceutical formulations and biological fluids. The proposed HPLC method was the first chromatographic method applied to estimate this mixture in a short chromatographic run (<6 min), high resolution between betrixaban/lercanidipine (Rs = 7.12) and acceptable values of limit of detection (LOD), limit of quantification (LOQ) and percentage of relative standard deviation (%RSD). The chromatographic separation was performed on a cyano column using a mobile phase composed of acetonitrile:methanol:water (35:35:30, v/v/v) containing 0.2% orthophosphoric acid adjusted to pH 3.2 by triethylamine, programmed with a flow rate of 1 mL/min with UV detection at 240 nm. The proposed method showed linearity over the concentration ranges of (0.20-20.0 µg/mL) and (0.25-25.0 µg/mL) for betrixaban and lercanidipine, respectively. All validation parameters met the acceptance criteria according to ICH guidelines in terms of linearity, LOD, LOQ, accuracy, precision, robustness, specificity and system suitability. The method was applied to assay the studied analytes in their pharmaceutical formulations with high % recovery (98-102%) and low %RSD (<1.5). Furthermore, the proposed method was successfully applied for the determination of betrixaban in spiked human plasma.

Circulating miR-146a expression predicts early treatment response to imatinib in adult chronic myeloid leukemia.

This study aimed to investigate the prognostic role of circulating miR-146a in the prediction of early response to imatinib treatment in patients with chronic myeloid leukemia (CML). Sixty patients with CML and 20 healthy controls were recruited in this study. BCR-ABL was assessed by quantitative rt-PCR at days 0 and 90 of imatinib therapy. Circulating miR-146a levels were assessed by quantitative rt-PCR at days 0, 14 and 90 of imatinib therapy for patients and once for controls. At day 90 of treatment, treatment response was achieved in 48 patients (80.0%). Responders had significantly lower baseline Sokal score when compared with non-responders. They also had significantly lower BCR-ABL expression at day 90 of treatment. The circulating miR-146a level was significantly lower in patients with CML than in healthy subjects and showed a significant rise after 14 days of imatinib treatment and an inverse correlation with BCR-ABL expression levels at 90 days. Using multivariate logistic regression analysis, baseline BCR-ABL (%) (OR (95% CI) 1.09 (1.03 to 1.016), p=0.006) and miR-146a at 14 days (OR (95% CI) 0.002 (0.0 to 0.09), p=0.001) were significant predictors of treatment response. Using ROC curve analysis, it was found that miR-146a expression at 14 and 90 days could distinguish responders from non-responders (AUC (95% CI) 0.849 (0.733 to 0.928) and 0.867 (0.755 to 0.941), respectively). This study reported for the first time that measurement of the circulating miR-146a expression at 14 days can predict the early response to imatinib treatment in patients with CML. Thus, this work indicates that miR-146a should be investigated in the setting of treatment response to other tyrosine kinase inhibitors.

First-derivative synchronous spectrofluorimetric method for estimation of losartan potassium and atorvastatin in their pure forms and in tablets.

Losartan potassium (LOS) and atorvastatin (ATR) are used in combination for long-term treatment of stroke and for treatment of hypertension with high-level cholesterol. Both drugs were simultaneously determined and validated using a novel, easy, fast, and economical first-derivative synchronous fluorescence spectroscopic method. Methanol was used as the solvent for both drugs at a Δλ 80 nm and with a scanning rate of 600 nm/min. Peaks were determined as at 288.1 nm and 263.6 nm for LOS and ATR, respectively. The proposed method was validated according to International Conference on Harmonization guidelines and, subsequently, the developed method was applicable to the analysis of the two compounds in their different formulations without interference from each other. Amplitude-concentration plots were rectilinear over the concentration ranges 1.0-10.0 µg/ml and 0.5-5.0 µg/ml for LOS and ATR, respectively. Detection limits were found to be 0.096 µg/ml and 0.030 µg/ml and quantitation limits were 0.291 µg/ml and 0.093 µg/ml for LOS and ATR, respectively. The proposed method was successfully applied to the analysis of both compounds in synthetic mixtures and in laboratory-prepared tablets. These results were in accordance with the results acquired using the comparison method, high-performance liquid chromatography.

Two validated spectrofluorimeteric and high performance liquid chromatography (HPLC) methods with fluorescence detection for the analysis of a new anti-hepatitis C drug, daclatasvir hydrochloride, in raw material or tablet form and in biological fluids.

Two sensitive and accurate methods have been developed for the estimation of daclatasvir (DAC) in its raw material, dosage form and in biological fluids. Method I is based on the measurement of DAC native fluorescence in methanol at 385 nm after excitation at 315 nm. The relationship between fluorescence intensity and concentration was found to be rectilinear over the linearity range (3.0-30.0 ng/ml). There were good per cent recoveries both in the dosage form (99.87 ± 0.84) and in spiked human plasma (99.96 ± 1.54%). Method II utilized reversed-phase high performance liquid chromatography to estimate the antiviral agent daclatasvir hydrochloride against hepatitis C within 4.0 min on a C18 column (Eurosphere. 100-5 C18, 150 × 4.6 mm, Germany) using a mobile phase consisting of acetonitrile and 0.1 M sodium dihydrogen phosphate (30:70, v/v) at pH 3.0 and with a fluorescence detector adjusted to 315 nm and 385 nm for excitation and emission respectively. The calibration curve was linear over the range (20.0-200.0 ng/ml) with SD 1.38%, error 0.56%, recovery 99.99 ± 1.30% in tablets, recovery 100.28 ± 1.73% in spiked urine and recovery 99.63 ± 2.72% in spiked plasma.The new developed methods were successfully applied to the assay of the daclatasvir in tablet form and extended to its determination in real plasma, spiked human plasma and urine. The analytical performance of the proposed method was validated according to International Conference on Harmonization (ICH) guidelines. The proposed methods were compared with the results of a comparison method and it was found that there was no significant difference between the methods, as revealed by Student's t-test and variance ratio F-test.

Green micellar HPLC analysis of three angiotensin-converting enzyme inhibitors in their mixtures with hydrochlorothiazide and modeling of their retention behavior by fitting to Foley's model.

We present an environmentally friendly method for the analysis of three angiotensin-converting enzyme inhibitors and hydrochlorothiazide simultaneously using a green micellar eluent for the first time. The chromatographic separation of enalapril maleate, lisinopril dihydrate, benazepril hydrochloride, and hydrochlorothiazide was implemented on an octadecyl silica column with a solution containing sodium dodecyl sulfate (0.12 M), 1-propyl alcohol (10% v/v), triethylamine (0.3% v/v), and H3 PO4 (0.02 M) at pH 3.6 as the mobile phase and UV detection at 210 nm. Validity of the method was confirmed and it exhibited good linearity within the ranges of 5.0-50.0 µg/mL for hydrochlorothiazide and 10.0-60.0 µg/mL for the three angiotensin-converting enzyme inhibitors with a limit of detection of 0.39 to 1.15 µg/mL for all the studied drugs. The developed micellar high-performance liquid chromatography method enables the quantification of the targeted angiotensin-converting enzyme inhibitors in combined tablets with hydrochlorothiazide by isocratic elution. There is no need for special precautions to prevent broadening and splitting of their chromatographic peaks. The method fulfills the society rights for safe and green analytical methods. The retention behavior of the four studied drugs was fitted to Foley's model and their association equilibria to the micelles (KAM ) and to the surface-modified stationary phase (KAS ) were calculated.

The impact of driving force on electron transfer rates in photovoltaic donor-acceptor blends.

The effect of acceptor energy level on electron transfer rate in blends of the polymer solar-cell material poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7) is studied using time-resolved fluorescence. Fast electron transfer in less than 2 ps is observed for a driving force between 0.2 and 0.6 eV and the electron transfer is slower outside this range. This dependence is described by Marcus theory with a reorganization energy of ≈0.4 eV.

Validated stability-indicating liquid chromatographic method for the determination of ribavirin in the presence of its degradation products: application to degradation kinetics.

Ribavirin was found to be liable to acidic, alkaline, oxidative and photolytic degradation. Hence, a simple, sensitive and stability-indicating reversed-phase liquid chromatographic method was developed and validated for the determination of ribavirin in the presence of its degradation products. The analysis was carried out on an ODS C18 (250 × 4.6 mm i.d.) stainless steel column using a mobile phase consisting of 0.02 M potassium dihydrogen phosphate. The analysis was performed at ambient temperature with a flow rate of 1 mL/min and UV detection at 207 nm. Pyridoxine hydrochloride was used as an internal standard. The method showed good linearity over the concentration range of 2.0-40 µg/mL with limit of detection of 0.34 µg/mL and limit of quantification of 1.03 µg/mL. The suggested method was successfully applied for the analysis of ribavirin in its commercial capsules. Statistical evaluation and comparison of the data obtained by the proposed and comparison method revealed good accuracy and precision of the proposed method. The drug was exposed to forced alkaline, acidic, oxidative and photolytic degradation according to the ICH guidelines. Moreover, the method was utilized to investigate the kinetics of alkaline and acidic degradation of the drug. The apparent first-order rate constants, half-life times and activation energies of the degradation process were calculated.