An ingenious technique based on the usage of fluorone-based dye; pyrosin B in prucalopride assay in different matrices through an "on-off" dye native fluorescence probe.

Prucalopride (PCD), is a modern medication approved by the United States in 2018 to alleviate constipation caused by motility issues. PCD demonstrates a strong affinity and selectivity toward the 5-HT4 receptor. The study here introduces a feasible, direct, non-extractive, and affordable pathway for PCD analytical tracking. The fluorimetric study is based on the on-off effect on the emission amplitude of fluorone-based dye (pyrosin B). In a one-pot experiment, the complex between PCD and pyrosin B is formed instantly in an acidic medium. Correlation between decreased pyrosin B emission and PCD concentrations provides a linear calibration plot from 50 to 900 ng/mL. PCD-dye complex system affecting variables were meticulously tuned. The values of the estimated limit of quantitation and limit of detection for the current methodology were 47.5 and 15.7 ng/mL, respectively. Conformity of the strategy validity was achieved by a comprehensive study of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use criteria. The method was convincingly applied for PCD assay in tablets and content uniformity investigation. Furthermore, PCD tracking in the spiked biological fluid was applied. Finally, the method uses distilled water as dispersing medium which rise accommodation with the green chemistry principle.

Facile and green chemistry-compatible fluorescence spectroscopic applications of acid red 87 used to evaluate eletriptan, antimigraine, in its pharmaceutical and biological samples.

Eletriptan (ETR), a selective pharmaceutical agent agonist of the 5-hydroxytryptamine1 receptor subtype, are primarily used to treat acute migraine attacks. ETR is a triptan-class medication that works by narrowing cerebral blood vessels and reducing chemicals that produce headache pain, light and sound sensitivity, and nausea. Due to its effectiveness in reducing migraine symptoms, it is a worthwhile choice for those looking for quick and efficient treatment. A green, raid, one-pot and straightforward fluorescence spectrometric method was employed to evaluate ETR in tablets and biological samples. By introducing the ETR drug and the fluorescent ligand, Acid red 87, in an acidic buffer, a quenching of the ligand native fluorescent was promptly produced. The quenching action was simply attributed to the selective ion-pair complex generation between the cationic target and the selected ligand. An increase in ETR concentration was linearly proportional to the quenching response in the 50.0 - 500.0 ng/mL range. The optimal configurations for adjusting the system's variable parameters were determined by examining the ETR-Acid red 87 system's response. Additionally, the sensor that was developed met the standards set by the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. The sensitivity thresholds of the approach were 13.8 and 42.0 ng/mL for the detection and quantification parameters, respectively, LOD and LOQ. This approach proficiently evaluated the pharmaceutical and biological samples of ETR. Finally, the proposed approach not only simplifies the analysis process but also limits the badimpact on the environment, making it a promising technique for analytical applications.

Synergistic utility of NBD-Cl fluorogenic loading activity and salting-out assisted liquid-liquid extraction as sample pretreatment in rasagiline tracking in different matrices.

A typical drug used to treat Parkinson's disease is called rasagiline. It belongs to an assortment of drugs known as monoamine oxidase inhibitors, which function by raising dopamine levels in the brain. This work created a unique spectrofluorimetric method for the analytical assay of rasagiline for the first time. The approach utilized the synergistic utility of the fluorogenic properties of benzofurazan and salting-out assisted liquid-liquid extraction. By combining these techniques an ultrasensitive, and highly selective methodology for the assay of rasagiline was established. Measurements were made of the resultant yellow fluorescent product at 533 nm by applying an excitation wavelength of 475.3 nm. The calibration graph was examined to assess its linearity across a range of 30-600 ng/ml. Through estimation, the limit of detection was discovered to be 8.9 ng/ml, while the quantitation limit was estimated to be 27 ng/ml. All relevant parameters influencing the fulfillment of the developed method were thoroughly examined and tuned. Following the directives set by the (ICH) the suggested approach was confirmed and demonstrated its capability for the accurate determination of rasagiline in tablets, as well as for testing content uniformity. The incorporation of salting-out assisted liquid-liquid extraction technology enables effective tracking of rasagiline in plasma samples, providing a novel and innovative approach for its analysis in biological matrices.

Nano-level assay of attention-deficit/hyperactivity disorder medicament, atomoxetine by molecular-size-based resonance rayleigh scattering strategy. Employment in content uniformity, dosage form, and plasma analysis.

The psychoanaleptic medication atomoxetine (ATX) is prescribed to cure attention-deficit hyperactivity syndrome. ATX works by selective prevention of norepinephrine reuptake. It acts by raising the brain's natural level of norepinephrine, which is necessary for behavior regulation. In this study, a sensitive and practical experimental method was employed to analyze the presence of ATX. The approach utilized a green chemistry-compatible technique, known as a one-pot experiment. The main principle behind this method was the use of molecular-size-dependant resonance Rayleigh scattering (RRS) phenomenon, which occurred due to the interaction between the dual complex of Cilefa Pink B and ATX. When ATX medication and Cilefa Pink B were combined in an acidic environment, they formed an association complex, leading to an amplification of the RRS signal. This amplification directly correlated with the concentration of ATX, specifically within the range of 40-1250 ng/mL. The RRS signal was monitored at a wavelength of 352 nm. The sensitivity of the method was demonstrated by the determination of the limit of detection (LOD) at 12.9 ng/mL and the limit of quantitation (LOQ) at 39.2 ng/mL. The variables of the method were thoroughly investigated and optimized. To ensure the reliability of the method, it was validated according to the International Council for Harmonisation (ICH) guidelines. Furthermore, the method was successfully applied to analyze ATX in its prescribed dosage form. The achievement of using the established resonance Rayleigh scattering (RRS) technology to analyze the target drug in plasma and ensure content uniformity was a remarkable feat.

Mathematical processing of absorption as green smart spectrophotometric methods for concurrent assay of hepatitis C antiviral drugs, Sofosbuvir and Simeprevir: application to combined pharmaceutical dosage forms and evaluation of the method greenness.

The present work was developed to create three rapid, simple, eco-friendly, cheap spectrophotometric methods for concurrent assay of Sofosbuvir (SOF) and Simeprevir (SMV) in their pure, laboratory prepared mixture and pharmaceutical dosage form with high degree of accuracy and precision. Three methods were developed including iso-absorptive point, ratio subtraction and dual wavelength. The linear range of the proposed methods was 3.0-50.0 and 2.0-50.0 µg mL-1 for SMV and SOF, respectively. The proposed methods were validated according to ICH guidelines in terms of linearity, accuracy, precision, limit of detection and limit of quantitation. The proposed approach is highly simple and the procedure is environmentally green making it suitable for the drug analysis in routine works.

A new application of isoindole fluorophore derivative in sitagliptin antidiabetic medication assay: Application to dosage forms and biological fluid evaluation.

Dipeptidyl peptidase-4 enzyme suppressant is a unique category of oral antidiabetic medication. Sitagliptin (STG) is a perfect member of this category and is pharmaceutically marketed alone or in combination with metformin. Here, the ideal application of an isoindole derivative for STG assay was developed using a feasible, easy-to-use, economic, and affordable method. STG as an amino group donor can form a luminescent derivative: isoindole on interaction with o-phthalaldehyde and the existence of (2-mercaptoethanol) 0.02% (v/v) as a thiol group donor. Excitation (339.7 nm) and emission (434.6 nm) wavelengths were used to monitor the isoindole fluorophore yield; moreover, each experimental variable was carefully investigated and adjusted. The calibration graph was constructed by plotting fluorescence intensities against STG concentrations, and controlled linearity was observed at concentrations ranging from 50 to 1000 ng/ml. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were analyzed in depth to prove the technique validation. The implementation of the present technique was extended successfully to the evaluation of various types of STG dose forms and spiking samples of human plasma and urine. The developed technique was shown to be an effective, simple, and quick replacement for quality control and clinical study evaluation of STG.

A novel spectrophotometric approach relies on a charge transfer complex between atomoxetine with quinone-based π-acceptor. Application to content uniformity test.

Atomoxetine (ATO) belongs to psychoanaleptic drugs and is utilized in attention-deficit hyperactivity syndrome treatment. In this study, two facile and selective approaches are implemented for the spectrophotometric analysis of atomoxetine. The two approaches rely on charge transfer formed between ATO base (n-donor) with p-chloranil and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ; π-acceptor). The generated complexes exhibit absorption intensity maxima at 550 and 460 nm in acetonitrile for p-chloranil and DDQ in the order. Under the optimum reaction condition, Beer's law was followed for p-chloranil and DDQ at concentrations of 30-320 and 10-80 µg mL- 1, respectively. The ICH guidelines were followed for work validation, and the outcomes were excellent and satisfactory. The assessment of ATO in pharmaceutical capsules using the suggested procedures was successful, and the results were contrasted with those obtained using a different published method to show accuracy and precision. Additionally, the two methods were used to assess the homogeneity of ATO content in the commercialized capsule.

An integrative analytical approach designed for feasible tranexamic acid assay using o-phthalaldehyde as a fluorogenic probe: applications to tablets, ampoules, and urine.

Antifibrinolytic tranexamic acid (TRX) suppresses plasminogen activation to plasmin in a competitive way. TRX is approved for the management of heavy menstrual periods, hereditary angioedema, hemophilia, postpartum hemorrhage, surgery, tooth extraction, and severe blood loss after acute trauma. Here, the practical use of an isoindole derivative was established for a novel, easy-to-use, and affordable TRX assay. In the presence of a molecule containing a sulfhydryl group (2-mercaptoethanol) 0.02% v/v, the primary amine moiety in TRX allows its combination with o-phthalaldehyde to produce a luminous product. Excitation (338.8 nm) and emission (433.9 nm) wavelengths were used to monitor the isoindole fluorophore yield, and each operational variable was carefully examined and adjusted. The calibration graph was constructed with fluorescence intensity versus TRX concentration, excellent linearity was observed at concentrations between 40 and 950 ng/ml, and limit of detection and limit of quantitation were 41.3 and 13.6 ng/ml, respectively. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were used to validate the method. The developed method for TRX assay in various dosage forms and urine was successfully implemented and was shown to be an effective, simple, and quick replacement for the TRX assay in clinical trials and quality control.

Application of isoindole fluorophore formation for determination of linagliptin in the sole and co-formulated tablets: Application for plasma assay and content uniformity testing.

Linagliptin is a new medicament belonging to dipeptidyl peptidase-4 enzyme inhibitors group. The mentioned medication is used to cure type 2 diabetes and is taken orally as a monotherapy or in a co-formulation with metformin. or empagliflozin. Herein, a novel, straightforward, and cost-effective method for linagliptin assay was developed with a workable use of an isoindole derivative. The primary amine moiety present in linagliptin enables its condensation with o-phthalaldehyde to form a fluorescent product in the presence of a sulfhydryl group-containing compound (2-mercaptoethanol) 0.01 % V/V. The isoindole fluorophore yield was monitored at (λexcitation 337.8 nm, λemission 434.3 nm) and all experimental variables were meticulously checked and adjusted. Fluorescence intensity versus linagliptin concentration was plotted to construct the calibration graph, and excellent linearity was achieved at values between 50 and 2000 ng/mL. The validity of the method was verified through a rigorous examination of the ICH guidelines. The method application was successful for linagliptin in different dosage forms, content uniformity study, and monitoring in spiked plasma. The devised technique was demonstrated to be a promising, easy, and quick alternate method for linagliptin assayin clinical study and quality control.

A specific turn-on fluorescence probe for determination of nitazoxanide based on feasible oxidation reaction with hypochlorite: Applying cobalt ferrite nanoparticles for pre-concentration and extraction of its metabolite from real urine samples.

Nitazoxanide is an antimicrobial compound that was originally developed as an antiprotozoal drug. Recently nitazoxanide has been identified as broad-spectrum antiviral agent and redirected for the remediation of some respiratory tract viral infections. In this study, the spectrofluorimetric technique has been applied to determine Nitazoxanide (NTX) in tablets or its metabolite, tizoxanide (TZD), in human urine samples. The developed methodology is based on oxidizing NTX (non-fluorescence) into a highly fluorescent product by sodium hypochlorite. The fluorescence emission intensity was measured at 436.5 nm after fluorescence excitation at 362.5 nm. After optimizing all conditions, the analytical procedures and bio-analytical steps were evaluated and validated using ICH and FDA criteria, respectively. The method linearity, LOQ, and LOD values of NTX were 1.0-5.0 µg/mL, 0.434, and 0.143 µg/mL, respectively. The other novelty side of the presented work is the application of cobalt ferrite (CoFe2O4) nanoparticles (NPs) as a magnetic solid-phase for the pre-concentration and extraction process. The synthesized magnetic nanoparticles were characterized by scanning electron microscope and zeta sizer techniques. Finally, the utilized magnetic nanoparticles exhibited good recovery results for pre-concentration and extraction of NTX or its metabolite from spiked and real human urine samples, respectively.

Two facile approaches based on association complex with erythrosine-B for nano-level analysis of duloxetine: application to content uniformity.

Duloxetine is an antidepressant that exhibits its action by preventing the reuptake of serotonin and norepinephrine by neurons. In this analytical study, we developed two facile, sensitive methods for duloxetine analysis. Both methods rely on the formation of binary association complex between erythrosine-B and duloxetine in an acidic medium using spectrofluorimetric and resonance Rayleigh scattering (RRS) techniques. Spectrofluorimetric method simply uses the quenching property of the formed complex on the native fluorescence of erythrosine-B at an emission wavelength of 557.2 nm (λ ex = 528.6), while RRS is based on detecting the enhancement in the RRS signal at 357.2 nm. The proposed methods have been validated according to the International Conference on Harmonization guidelines. The approaches provide linear assay of duloxetine hydrochloride over 0.1-2.4 µg ml-1 and 0.2-2.0 µg ml-1 for spectrofluorimetric and RRS methods, respectively. Variables affecting methods and complex formation were studied and optimized. The limit of detection values were 0.03 and 0.056 µg ml-1 for spectrofluorimetric and RRS methods, respectively. Both approaches were applied with acceptable results for formulation analysis and evaluation of cymbatex capsule content uniformity.

Investigation of the association complex formed between dapoxetine and erythrosine-B for facile dapoxetine assay in pharmaceutical formulation using resonance Rayleigh scattering and spectrofluorimetric techniques.

Premature ejaculation is a male sexual problem that is marked by rapid ejaculation and quick attainment of orgasm. Dapoxetine belongs to the antidepressant category and modulates its action by preventing the reuptake of serotonin by neurons. Dapoxetine is marketed as an off-label therapy for premature ejaculation. Here, two facile, sensitive, and green compatible approaches were established for dapoxetine assay. The approaches chemically rely on association complex formed between erythrosine-B and dapoxetine in an acidic buffered medium. The quenching effect of the formed complex on the native erythrosine fluorescence at emission 553.5 nm is simply the main idea of spectrofluorimetric assay, while resonance Rayleigh scattering methodology uses augmentation of resonance Rayleigh scattering spectrum at 345 nm by the added dapoxetine. The current approaches exhibit linearity between response and dapoxetine concentration over 0.2-2.5 µg/ml and 0.3-3.0 µg/ml for spectrofluorimetric and resonance Rayleigh scattering (RRS) methods, respectively. All variables affecting methods and complex formation were studied and precisely optimized. The criteria of validation were performed by the directives provided by International Conference on Harmonization's (ICH) Guidelines and limits of detection were 0.06 and 0.05 µg/ml for spectrofluorimetric and RRS techniques, respectively. Finally, the approaches were applied with acceptable results for pharmaceutical formulation analysis.

A new convenient methodology based on dihydropyridine derivative for selective fluorimetric analysis of baclofen: Application to spiked urine and content uniformity evaluation.

Baclofen belongs to skeletal muscle relaxant and is used for the treatment of muscle spasticity that originated from multiple sclerosis or a spinal cord injury and other cases as hiccups. In the current analytical study, a new, convenient and selective fluorimetric method for baclofen analysis has been developed and validated. The analytical methodology depends on Hantzsch reaction that leads to formation of dihydropyridine fluorescent derivative. The primary amino moiety in baclofen condensed with two equivalents of acetylacetone in the presence of formaldehyde and acetate buffer solutions. Spectrofluorimetric monitoring of the product was accomplished at emission wavelength of 477.3 nm after excitation at 419.9 nm. The method exhibited linearity when baclofen concentration plotted against the fourescence response in the range of 0.3-6.0 µg/mL. Adjustment of the reaction variables and studying validation parameters according to directives of ICH were performed perfectly. Ultimately, the proposed approach was applied successfully for baclofen analysis in raw material, dosage form and spiked urine and it was also extended to test content uniformity.

A new feasible approach based on utility of ninhydrin for selective fluorimetric analysis of baclofen. Application to content uniformity evaluation.

In the current proposed analysis, a new, feasible, and selective fluorimetric approach was designed for baclofen assay. Baclofen is a medication prescribed as a therapy for muscle spasticity that originated from multiple sclerosis or a spinal cord injury, and other cases such as hiccups. The analytical approach relies on the use of ninhydrin to form a fluorescent derivative that was monitored at λex 386 nm or λem 480 nm. Under suitable reaction conditions, the primary amino moiety in baclofen was condensed with ninhydrin and phenylacetaldehyde in the presence of Teorel buffer as a buffered medium. The method exhibited linearity when baclofen concentration was plotted against response in the range 1-10 µg ml-1 . Adjustment of the reaction variables and study of validation parameters according to ICH directives were performed correctly. An interference study was implemented to ensure that no discrepancy from the excipient had occurred. Finally, the proposed method was applied successfully for baclofen assay in dosage form and extended to test Mylobac content uniformity.

Use of acetylacetone for nano-level assay of fluvoxamine maleate in pure form and pharmaceutical formulation.

The present study developed and validated a selective spectrofluorimetric method designed to assay fluvoxamine maleate (FLX). The validated method relied on the condensation reaction between FLX and acetylacetone/formaldehyde using acetate buffer (pH 4.2). The formed fluorescent product was measured at an emission wavelength of 479 nm after excitation at 419 nm. Parameters that influenced the reaction were studied and adjusted accurately. The constructed calibration graph was rectilinear over the range 200-2000 ng ml-1 and the estimated limit of detection was 60 ng ml-1 . Two products from an Egyptian market were assayed using the suggested method and the final results agreed with the measurements of the reported method. The selectivity of the proposed approach was evaluated using the standard addition method and results were acceptable and confirmed the reliability of this approach. Finally, directives from the International Council for Harmonisation guidelines were applied to establish the validity of the study.

One-pot micellar augmented native fluorescence for facile fluorimetric assay of dapoxetine hydrochloride in biological plasma and tablets.

One of the medical problems is premature ejaculation which characterized by quick ejaculation and reaching orgasm rapidly. Dapoxetine was accepted as off-label antidepressant used in the treatment of premature ejaculation, so hereby we provide an innovative, non-extractive, environmentally safe protocol for the assay of dapoxetine in biological plasma and tablet. The principle of the assay is simple and only based on native fluorescence which was enhanced by micelle. Parameters influencing the method were optimized and measurements were accomplished at emission wavelength of 338 nm after excitation at 294 nm. The fluorescence-concentration plot was rectilinear over the range of 0.1-4 µg/mL. Directives of ICH guideline were the rules which followed to ensure the validity of the work. Eventually, the procedure was utilized in the dosage form assay and extended to include biological plasma analyses, with good percentage recuperation.

One-pot reaction for determination of Asenapine maleate through facile complex formation with xanthine based dye: Application to content uniformity test.

Asenapine maleate was approved by the FDA for the treatment of schizophrenia and mania or mixed episodes with bipolar I disorder. In the present article, two spectroscopic methods were developed and validated for the determination of asenapine. Both methods depend on association complex formation between xanthine based dye (eosin Y) and the cited drug in acetate buffer pH = 3.8. In the spectrophotometric method (method I), the absorbance of the formed complex was estimated at maximum wavelength of 545 nm and Beer's law was obeyed in the range of 1-12 µg mL-1. The spectrofluorimetric method (method II) depends on measuring the quenching effect of the drug on the native fluorescence of eosin Y at 545 nm after excitation at 303 nm. The linearity range of method II was 0.4-3.2 µg mL-1. The limits of detection were 0.24 and 0.08 µg mL-1 for method I and II, respectively. The instructions of ICH were followed to fully validate the developed analytical procedures. The formation constant of the reaction was 3.93 × 104 while its Gibb's free energy was -2.6 × 104 J mol-1. Finally, the methods were applied for the analysis of pharmaceutical tablets and for evaluation of their content uniformity.

New approach for stability study and determination of fluvoxamine in raw materials and pharmaceuticals through condensation with 2,2-dihydroxyindane-1,3-dione.

The present study describes the validation of a selective spectroscopic method for assay of fluvoxamine maleate (FXM). The validated method relies on condensation of FXM with 2,2-dihydroxyindane-1,3-dione and phenylacetaldehyde using Teorell-Stenhagen buffer (pH 6.6) to give coloured fluorescent product measured at 482 nm using 386 nm as the excitation wavelength. The parameters influencing the reaction were studied precisely and adjusted accurately. The constructed calibration graph appeared rectilinear over the following range (0.8-14 µg ml-1 ) and the estimated limit of detection was 0.25 µg ml-1 . Two pharmaceutical products from the Egyptian market were assayed using the suggested method and the final results agreed with measurements from other reported methods. Moreover, the drug was subjected to diverse stress conditions including acidic, alkaline, thermal, and photolytic degradation to examine the FXM stability. Directives from the International Conference on Harmonisation guidelines were applied to establish the validity of the work.

A new approach based on isoindole formation reaction for sensitive fluorimetric assay of milnacipran in tablets and biological fluids (plasma/urine).

The current study describes a new, sensitive, and economic protocol for milnacipran analysis. Milnacipran was introduced as a therapy for fibromyalgia and depression. It acts by unique and equal inhibition of noradrenaline and serotonin neurotransmitters reuptake. In the presence of 2-mercaptoethanol, the amino moiety of milnacipran condenses with o-phthalaldehyde to generate isoindole fluorescent derivative. The isoindole product was measured at (λ ex 338.5 nm, λ em 433.5 nm) and condensation variables were strictly optimized. The fluorescence intensity of measurements was plotted versus milnacipran concentration to give a linearity range over 200-4000 ng mL-1. The proposed approach was fully validated by the directives of ICH guidelines and applied without any influence of combined excipient for milnacipran tablet analysis. Furthermore, the procedure was applied in spiked urine and plasma analysis with excellent percentage recovery.

Studying the association complex formation of atomoxetine and fluvoxamine with eosin Y and its application in their fluorimetric determination.

A simple, sensitive and non-extractive spectrofluorimetric method has been developed and validated for the determination of two psychoanaleptic drugs, atomoxetine and fluvoxamine, in pure forms and pharmaceutical dosage forms. The proposed method is based on the formation of binary complexes between eosin Y and the studied drugs in the presence of a Teorell-Stenhagen buffer. The quenching of the native fluorescence of eosin Y due to complex formation with the studied drugs was measured spectrofluorimetrically at 545 nm after excitation at 302 nm. At the optimum reaction conditions, the fluorescence quenching values (ΔF) and concentrations were rectilinear over the concentration ranges of 0.2-2.2 and 0.3-2.2 µg ml-1 for atomoxetine and fluvoxamine, respectively. The developed method was successfully applied for the determination of the studied drugs in their pharmaceutical formulations with average percentage recoveries of 100.13 ± 0.66 and 99.69 ± 0.44 for atomoxetine and fluvoxamine, respectively (n = 5), without interference from common excipients.