Content uploaded by Fawzia Ibrahim
Author content
All content in this area was uploaded by Fawzia Ibrahim on Jan 15, 2021
Content may be subject to copyright.
A preview of the PDF is not available
Assessment of two analgesic drugs through fluorescence quenching of acriflavine as a new green methodology
Abstract
Two non-steroidal anti-inflammatory drugs, ketoprofen and diclofenac sodium could be determined spectrofluorimetrically in their pure forms and different dosage forms using acriflavine reagent. It was found that the quenching of acriflavine fluorescence is going linearly with increasing the concentration over the ranges of 1.0-10.0 μg/mL for both ketoprofen and diclofenac sodium. The proposed method was studied to attain the optimum conditions with maximum sensitivity and precision without harming the environment. A proposal for the reaction mechanism was postulated depending on ion-association complex formation between acriflavine and each of the studied drugs in 1:1 ratio. International council of harmonization (ICH) guidelines were followed to validate the method. The lowest amount that could be detected by the proposed method is 0.28 and 0.48 μg/mL for both ketoprofen and diclofenac sodium, respectively. It was found that no significant difference between the proposed and comparison methods as indicated from the calculated statistical values.
... In method IV, acriflavine has been used as a fluorescent quenching reagent for the determination of erdosteine. Acriflavine is a dye that has been previously used as a fluorogenic reagent for the quantitation of various drugs, such as ascorbic acid, ketoprofen, acemetacin and tranilust [31][32][33][34][35] . This chemical reaction relies on the ability of the drug to quench the acriflavine fluorescence quantitively allowing for accurate drug determination. ...
... Dynamic quenching is due to interaction of the excited state of the fluorophore with the quencher which results in radiationless deactivation of the fluorophore to the ground state. While static quenching occurs when the fluorophore and the quencher form a complex in the ground state, i.e. before excitation occurs [31][32][33][34][35] . It is possible for the quenching to occur through different mechanisms; such as emission group destruction, molecular rearrangements, energy/electron transfer…etc [31][32][33][34][35] . ...
... While static quenching occurs when the fluorophore and the quencher form a complex in the ground state, i.e. before excitation occurs [31][32][33][34][35] . It is possible for the quenching to occur through different mechanisms; such as emission group destruction, molecular rearrangements, energy/electron transfer…etc [31][32][33][34][35] . In order to clarify the potential quenching mechanism, the following Stern-Volmer Equation was followed where F 0 and F stands for the fluorescence intensities in the absence and presence of drug, respectively, K sv refers to the Stern-Volmer quenching constant, and [ERD] is the drug molar concentration. ...
Four simple, sensitive, economical, and eco-friendly spectrophotometric and spectrofluorimetric methods for the assay of erdosteine (ERD) in bulk and dosage form have been developed and validated as per the current ICH guidelines. Method I involved the addition of the powerful oxidizing agent, potassium permanganate to ERD and measuring the oxidation product at 600 nm. Another oxidizing agent; ceric ammonium sulfate was used in Method II where ERD is oxidized resulting in a decline in the absorbance intensity of cerium (IV) ions, measured at 320 nm. Similarly, Method III employed the use of ceric ammonium sulfate, However, the fluorescence intensity of the resulting cerium (III) ions was recorded at λex/λem 255/355 nm, respectively. Whereas in Method IV, ERD was added to acriflavine leading to a proportional decrease in its native fluorescence. Various reaction conditions affecting the intensity of measurement were attentively investigated, optimized, and validated. All the suggested methods did not require any tedious extraction procedures nor organic solvents. The implementation of the proposed methods in ERD assay resulted in linear relationships between the measured signals and the corresponding concentrations of ERD in the range of 1–6, 0.1–1.0, 0.01–0.1, and 10–100 μg/mL with LOD values 0.179, 0.024, 0.0027 and, 3.2 μg/mL for methods I, II, III and IV respectively. The suggested methods were successfully applied to ERD analysis in pure form and in commercial capsules. Furthermore, the eco-friendliness of the proposed methods was thoroughly checked using various greenness testing tools. Lastly, this work, not only presents highly sensitive, green, mix-and-read methods for ERD determination, but also, describes the determination of ERD spectrofluorimetrically for the first time in the literature.
... A review of the literature revealed numerous analytical approaches for determining DCF. Among these approaches are spectrophotometry [4][5][6][7], spectrofluorimetry [8,9], gas chromatography [4], chromatography [10][11][12][13][14][15][16]. These techniques have been used to detect DCF in medicinal and biological fluids. ...
The current work suggests a new, ultrasensitive green functionalized sensor for the determination of anti-inflammatory medication diclofenac sodium (DCF). Alumina (Al2O3) and cerium oxide (CeO2) nanoparticles (NPs) have attracted great interest for their use as outstanding and electroactive nanocomposite in potentiometric and sensory research due to their ultrafunctional potential. The formed nanoparticles have been confirmed using various spectroscopic and microscopic techniques. The fennel extract-mediated Al2O3/CeO2 nanocomposite (Al2O3/CeO2 NCS) modified coated wire membrane sensor developed in this study was used to quantify DCF in bulk and commercial products. Diclofenac sodium was coupled with phosphomolybdic acid (PMA) to generate diclofenac phosphomolybdate (DCF-PM) as an active ion-pair in the existence of polyvinyl chloride (PVC) and o-nitrophenyl octyl ether (o-NPOE). Clear peaks at 270, and 303 nm with band gaps of 4.59 eV and 4.09 eV were measured using UV–vis spectroscopy of Al2O3 and CeO2, respectively. The crystallite sizes of the formed nanoparticles were XRD-determined to be 30.13 ± 8, 17.72 ± 3, and 35.8 ± 0.5 nm for Al2O3, CeO2, and Al2O3/CeO2 NCS, respectively. The developed sensor showed excellent response for the measurement and assay of DCF, with a linearity between 1.0 × 10⁻⁹ and 1.0 × 10⁻² mol L⁻¹. EmV = (57.76) log [DCF] +622.69 was derived. On the other hand, the typical type DCF-PM presented a potentiometric response range of 1.0 × 10⁻⁵-1.0 × 10⁻² mol L⁻¹ and a regression equation of EmV = (56.97) log [DCF]+367.16. The functionalized sensor that was proposed was successful in determining DCF in its commercial tablets with percent recovery 99.95 ± 0.3. Method validation has been used to improve the suitability of the suggested potentiometric technique, by studying various parameters with respect to the international council harmonization requirements for analytical methodologies.
... Depending on the conditions (pH, type of solvent, etc.), acriavine may interact through hydrogen bonding, van der Waals, ionic and hydrophobic bonds. For example acriavine is known to form ion pair complexes via electrostatic interactions with such the drugs as ketoprofen, diclofenac sodium, 35 tranilast, 36 olsalazine and sulfasalazine. 37 Moreover, acriavine can form an ion association complex with tartrazine in an acidic environment at pH 3.75, due to the presence of a carboxyl group in the structure of these drugs, where acriavine can dissociate as a positively charged cation (-N + ), and tartrazine can exist as two negatively charged anions (-SO 3− ). ...
Cancer is a global health problem being the second worldwide cause of deaths right after cardiovascular diseases. The main methods of cancer treatment involve surgery, radiation and chemotherapy with an emphasis on the latter. Thus development of nanochemistry and nanomedicine in a search for more effective and safer cancer treatment is an important area of current research. Below, we present interaction of doxorubicin and acriflavine and the cytotoxicity of these drug nano-complexes towards cervical cancer (HeLa) cells. Experimental results obtained from NMR measurements and fluorescence spectroscopy show that the drugs' interaction was due to van der Waals forces, formation of hydrogen bonds and π-π stacking. Quantum molecular simulations confirmed the experimental results with regard to existing π-π stacking. Additionally it was shown that, at the level of theory applied (DFT, triple zeta basis set), the stacking interactions comprise the most preferable interactions (the lowest ΔG ca. -12 kcal mol-1) both between the molecules forming the acriflavine system and between the other component - another drug (doxorubicin) dimer. Biological tests performed on HeLa cells showed high cytotoxicity of the complexes, comparable to free drugs (ACF and DOX), both after 24 and 48 hours of incubation. For non-cancerous cells, a statistically significant difference in the cytotoxicity of drugs and complexes was observed in the case of a short incubation period. The results of the uptake study showed significantly more efficient cellular uptake of acriflavine than doxorubicin, whether administered alone or in combination with an anthracycline. The mechanism determining the selective uptake of acriflavine and ACF : DOX complexes towards non-cancer and cancer cells should be better understood in the future, as it may be of key importance in the design of complexes with toxic anti-cancer drugs.
... In addition, it has been also approved by the U.S. Food and Drug Administration (FDA) as a safe drug for the topical treatment of wounds. 1 ACF is a mixture of 3,6-diamino-10-methylacridine chloride (trypaflavine) and 3,6-diaminoacridine (proflavine) (Figure 1). 2 Its biological activity is attributed to the fact that it effectively intercalates with deoxyribonucleic acid (DNA). 3−6 As a result, it has the ability to interfere with many cellular functions. ...
Acriflavine (ACF) has been known for years as an antibacterial drug. The identification of key oncogenic mechanisms has brought, in recent years, a significant increase in studies on ACF as a multipurpose drug that would improve the prognosis for cancer patients. ACF interferes with the expression of the hypoxia inducible factor, thus acting on metastatic niches of tumors and significantly enhancing the effects of other anticancer therapies. It has been recognized as the most potent HIF-1 inhibitor out of the 336 drugs approved by the FDA. This work presents up-to-date knowledge about the mechanisms of action of ACF and its related prodrug systems in the context of anticancer and SARS-CoV-2 inhibitory properties. It explains the multitask nature of this drug and suggests mechanisms of ACF's action on the coronavirus. Other recent reports on ACF-based systems as potential antibacterial and antiviral drugs are also described.
... 19 It has recently been utilized as a uorescent reagent for the estimation of a variety of drugs, such as ascorbic acid, 20 ketoprofen, and diclofenac sodium. 21 This chemical reaction is based mainly on the quenching of its uorescence in a quantitative way that could permit drug determination. ...
Tranilast (TR) could be investigated as a suitable anti-inflammatory and NLRP3 inflammasome inhibitor medication for the treatment of COVID-19 acute patients. Owing to its importance, our study was constructed for the determination of TR using a new, fast, sensitive, and reliable green spectrofluorimetric method. TR was quantified in this study by forming a complex with the acriflavine (AC) reagent. The reaction between TR and AC quenched the fluorescence of AC through the formation of an ion-association complex and the response was measured at 493 nm after excitation at 263 nm. It was observed that the quenching of the fluorescence of AC was linear (r = 0.9998) with the concentration of TR in the range of 1.0-15.0 μg mL-1. The limit of detection was 0.224 μg mL-1, and the limit of quantification was 0.679 μg mL-1. The fluorescence quenching mechanism was carefully studied and was confirmed to be able to analyze TR in its pure form and its prepared pharmaceutical dosage form. To validate the method, the international conference of harmonization (ICH) Q2R1 guidelines were followed. The statistical assessment of the proposed and comparison methods revealed no significant differences between them. Moreover, the green criteria of the method were evaluated and confirmed.
The non-steroidal anti-inflammatory medication acemetacin was assessed via two straightforward green spectrofluorimetric techniques. The quenching-dependent derivatizing spectrofluorimetric reactions are the master point of this study. Acriflavine-based method (Method I) depends on forming an ion association complex between acriflavine and the drug in a ratio of 1:1, decreasing the former's fluorescence intensity. Acriflavine or Ag NP's intensity-related quenching action goes linearly with the acemetacin concentration in the 2.0–20.0 µg/mL and 1.0–16.0 µg/mL ranges, respectively. The second quenching mechanism depends on using the silver nanoparticles (Ag NP's) as a fluorescence probe (Method II); Ag NP's were prepared from reducing silver nitrate using sodium borohydride. Both methods could be applied to determine pure and pharmaceutical dosage forms of acemetacin. The methods proved valid according to the international conference on harmonization (ICH) guidelines. In addition to this, this work has been estimated under green criteria assessment tools. There is no significant difference between the proposed and the comparison methods after the statistical interpretation.
Ketoprofen (2-(3-benzoylphenyl)-propionic acid) is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic actions, that make it valuable in the treatment of rheumatoid arthritis and to relieve mild to moderate pain (Medina-López, Vara-Gama, Soria-Arteche, Moreno-Rocha, & López-Muñoz, 2018) . The widespread and growing medical application needs to be followed by the development of analytical techniques for detection of ketoprofen traces in various body fluids or wastewaters.
Simple, inexpensive, rapid and sensitive determination of furosemide spectrofluorometrically was suggested using acriflavine as a new reagent. The method based on the quantitative quenching effect of furosemide on the native fluorescence of acriflavine in presence of Britton-Robinson buffer medium due to the reaction of furosemide with acriflavine to form an ion associated complex. The decrease of acriflavine fluorescence was observed at 505 nm after excitation at 265 nm. the florescence – concentration plot is rectilinear over the range of 2.0-10 µg/ml with correlation coefficient 0.9991 and detection limit 0.2 µg/ml. No interference was observed from the excipients that are commonly present in pharmaceutical formulations. The proposed method was determination of furosemide in some commercial tablets. The results were compared with that of HPLC method revealed with good agreements and no significant differences in the accuracy and precision.
Fluorescence quenching method is exploited to determine the caffeine content of coffee beans in water solution. This method is based on correlating the decrease in fluorescence intensity of rhodamine molecule due to the quenching effect of caffeine, which is due to the energy transfer from an excited rhodamine (donor) molecule to coffee or caffeine (acceptor) molecule. The decrease in rhodamine fluorescence intensity is found to be a linear function of caffeine concentration. The concentration range is from 1.0 × 10-5 mol/ L of caffeine in 2.85 × 10-6; mol/L of rhodamine solution to 5 × 10-5 mol/L of caffeine in 2.85 × 10 -6 mol/L of rhodamine solution. The caffeine content of coffee was determined and its value is 0.95 ± 0.01%. The results found in this method have a very good correlation with the results determined using established methods. Further, the mechanism of quenching was studied using IR spectroscopy and the result indicates that the carbonyl groups (C=O) are the functional groups that play a prominent role in caffeine dye interaction.
In the current study, a method for the determination of sulfasalazine (SSZ) based on the fluorescence quenching of Tb-2,6-pyridinedicarboxylic acid (Tb-DPA) complex probe in the presence of sodium dodecylbenzene sulfonate (SDBS) was established. Moreover, the mechanism of fluorescence quenching was studied and it was concluded that the process is static quenching and involved the formation of the SSZ-Tb-DPA ternary complex. Under the optimum conditions, the linear range of the method was 8.0 × 10⁻⁸–1.00 × 10⁻⁶ M and 1.00 × 10⁻⁶–1.00 × 10⁻⁴ M with the detection limit of 60 nM. The approach was successfully applied for the detection of SSZ in pharmaceutical preparations, urine, and human serum samples with recoveries between 98% and 106%.
An easily performed, specific, sensitive, rapid, reliable and inexpensive procedure for the spectrofluorometric quantitation of ascorbic acid was proposed using acriflavine as a fluorescence quenching reagent. The procedure was based on the determined quenching effect of ascorbic acid on the natural fluorescence signal of acriflavine and the reaction between ascorbic acid and acriflavine in Britton–Robinson buffer solution (pH 6) to produce an ion‐associated complex. The reduction in acriflavine fluorescence intensity was detected at 505 nm, while excitation occurred at 265 nm. The relationship between quenching fluorescence intensity (∆F) and concentration of ascorbic acid was linear (R² = 0.9967) within the range 2–10 μg/ml and with a detection limit of 0.08 μg/ml. No significant interference was detected from other materials often found in pharmaceutical nutritional tablets. The obtained results were compared with those from high‐performance liquid chromatography and appeared in good agreement, with no important differences in precision or accuracy. The proposed spectrofluorimetric method was used to determine the amount of ascorbic acid in a number of commercial pharmaceutical nutritional supplement tablets with a 95% confidence performance.
A simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of sitagliptin phosphate (STP) and saxagliptin (SAX). The proposed method is based on Hantzsch reaction of both drugs through their reaction with acetyl acetone-formaldehyde reagent (AAF) followed by investigation of the fluorescence spectral behavior of the formed fluorescent products in presence of Sodium Dodecyl Sulfate (SDS) micellar system as additive to enhance the obtained flourescence at 483 nm after excitation at 419 nm for both drugs. The fluorescence intensity in the presence of SDS increased by 1.7 and 1.6 folds for STP and SAX, respectively than that of the surfactant free aqueous. The linearity of calibration curve was found at range of 50–700 ng mL⁻¹ and 150–900 ng mL⁻¹ with detection limits of 16.43 and 38.60 ng mL⁻¹ for STP and SAX, respectively. The percent recovery ± standard deviation was found to be 99.87 ± 0.77 and 99.00 ± 0.52 for STP and SAX, respectively. The values of relative standard deviations were below 2% indicating good precision of the developed method. The analysis of the studied drugs in bulk, spiked human plasma, dosage form and content uniformity test was successfully applied with high accuracy.
In this paper, the modeling and the optimization of the removal efficiency of ketoprofen (KTP) by the electrocoagulation process were studied. The central composite design experiments (CCD) method was used to study the main effects and the interaction effects between operational parameters and to optimize the value of each parameter. According to the regression equation obtained, the current density appears to be one of the most important parameters (b2 = +22.11) controlling the removal efficiency of KTP. The positive sign of b2 coefficient suggests that the increase of current density increases the yield of removal. The second significant parameter with a negative effect was the initial KTP concentration (b3 = −16.27). This result suggests that the removal efficiency was inversely proportional to the initial concentration. In addition, according to the model, the most influencing interactions were pH-current density, pH-initial concentration, and current density-initial concentration. The model obtained by CCD led to the following optimal conditions for KTP removal efficiency (96.70%): pH = 7, i = 24.04 mA cm⁻², and C0 = 5 mg L⁻¹.
Simple, sensitive, selective, precise stability indicating chromatographic methods for determination of Drotaverine Hydrochloride and Diclofenac Potassium from pharmaceutical tablets were developed and validated as per the ICH guidelines. A novel stabilityindicating LC assay method was developed and validated for quantitative determination of Drotaverine and Diclofenac in bulk drugs and in pharmaceutical dosage form. An isocratic, reversed phase LC method was developed using an Qualisil BDS C8 column (250 mm × 4.6 mm, 5.0 μ particle size), using methanol: THF: acetate buffer (45:08:17 v/v) pH adjusted to 5.0 with acetic acid mobile phase, flow rate was 0.7 mL min -1 and column was maintained at 50 °C. The detection was carried out at 292 nm and injection volume was 20 μL. The peak purity was checked with the photodiode array detector. Drotaverine Hydrochloride and Diclofenac Potassium were subjected to acid, alkali and neutral hydrolysis, oxidation, photo degradation and dry heat and wet heat treatment. Degradation products were well separated from the analytes peaks. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. The developed method was validated with respect to linearity, accuracy (recovery), precision, specificity and robustness.
A fast and reliable high performance liquid chromatography method for determination of paracetamol, chlorzaxozone and diclofenac potassium has been developed. The chromatographic method was standardised using a reverse phase C18 column with UV-VIS detector at 254 nm. Mobile phase consisted of methanol-0.01M monobasic sodium phosphate with equal volume of 0.01M ortho phosphoric acid (70:30) (p H adjusted to 2.5 ± 0.2 using 10% orthophosphoric acid) at a flow rate 1 ml/min. The method was validated and produced accurate and precise result for these drugs.
Objective: Research study was undertaken to develop and validate simple, rapid, precise, accurate, robust High Performance Thin Layer Chromatographic (HPTLC) method for simultaneous determination of paracetamol (PARA), diclofenac potassium (DCL) and chlorzoxazone (CHL) in bulk drug and tablet dosage form. Methods: The chromatographic separation was performed on precoated silica gel G 60 F254 plates with toluene: ethyl acetate [55:45, v/v] as mobile phase. The detection was carried out at 271 nm. Results: Retention factors of PARA, DCL and CHL were found to be 0.21 ± 0.01, 0.54 ± 0.01, and 0.74 ± 0.01, respectively. Linearity of PARA, DCL and CHL was found to be in the concentration range of 1000-3500 ng band-1, 100-350 ng band-1 and 500-1750 ng band-1, respectively. The % assay (Mean ± S.D.) was found to be 100.63 % ± 1.2, 103.46 ± 1.58 and 101.85 % ± 1.92 for PARA, DCL and CHL, respectively. Method was validated for linearity, accuracy, precision, specificity, robustness in accordance with International Conference on Harmonisation [ICH] guidelines. Conclusion: The proposed HPTLC method has been successfully applied for the analysis of drugs in tablet dosage formulation and applicable to routine analysis PARA, DCL and CHL in bulk drug and tablet dosage form.