Integrated resonance Rayleigh scattering approach utilizing Box-Behnken experimental design for the facile quantification of prucalopride in pharmaceutical tablets and human urine with sustainability assessment.

Prucalopride (PCP) is one of the recent drugs used for the regulation of gastrointestinal tract motility and the treatment of constipation. A new, highly sensitive and fast resonance Rayleigh scattering (RRS) approach was suggested for PCP determination. The approach was based on its reaction of PCP with eosin Y in buffered medium (pH 3.5) to form an ion pair association complex which had a significant enhancement in RRS compared to that of eosin Y or PCP alone. The enhancement of RRS intensity had straight correlation to PCP concentration ranging from 150 to 2000 ng mL-1 with 38 ng mL-1 as LOD and 125 ng mL-1 as LOQ. The measurements were done at a wavelength of 365 nm that provided the maximum sensitivity. All the experimental parameters were studied carefully and optimized via Box-Behnken experimental design. The International Council for Harmonization (ICH) guidelines were employed to validate the suggested method and the obtained results proved the appropriate method performance. The method was efficiently utilized to determine PCP in pure form, pharmaceutical tablets and spiked urine samples with no interferences from the surrounding matrices. Furthermore, the greenness of the suggested procedure was confirmed using different green metric approaches.

Determination of antihistaminic drugs alcaftadine and olopatadine hydrochloride via ion-pairing with eosin Y as a spectrofluorimetric and spectrophotometric probe: application to dosage forms.

Four sensitive and fast analytical approaches relied on ion pairing with eosin Y were built up and evaluated using spectroscopy for determination of Alcaftadine and Olopatadine hydrochloride with high sensitivity and selectivity. Two spectrofluorimetric techniques were employed to observe the quenching effect of Alcaftadine or Olopatadine hydrochloride on the intrinsic fluorescence of eosin Y in a 0.1 M acetate buffer solution at pH 3.8 and 3.3 for Alcaftadine and Olopatadine hydrochloride, respectively. Those methods are considered the first spectrofluorimetric methods for Alcaftadine and Olopatadine hydrochloride assay. The fluorescence quenching effect was linear with concentration ranging from 150 to 2000 and 200 to 2000 ng mL-1 for Alcaftadine and Olopatadine hydrochloride, respectively. In the two spectrophotometric techniques, the absorbance of the produced ion-pair was monitored at 548 and 547 nm in aqueous buffered solution at pH 3.8 and 3.3 for Alcaftadine and Olopatadine hydrochloride, respectively. Beer's law was obeyed in the concentrations range of 0.8-8.0 and 1.0-10.0 µg mL-1. The four techniques were evaluated in accordance with ICH requirements and were effectively used to analyze dosage forms with a high percent recovery.

An eco-friendly one-pot spectrofluorimetric approach for the facile determination of overactive bladder drug, tolterodine: Application to dosage forms and biological fluids.

Tolterodine tartrate (TTD) was the first antimuscarinic medication developed exclusively for the treatment of overactive bladder syndrome and was approved by the FDA in 1998. As a result of the drug's extensive utilization within the local community following its authorization, there is a pressing need to develop and validate a spectrofluorometric method that is economically efficient, easily reproducible, environmentally sustainable, and possesses high sensitivity. The developed approach relies on enhancing the fluorescence intensity of TTD to reach a level 720 % higher than its initial value, achieved through the application of an aqueous sodium dodecyl sulfate (SDS) solution. A strong correlation was observed with a correlation coefficient of 0.9998 between the concentration of TTD and the fluorescence intensity within the range of 25.0-500.0 ng mL-1. This approach could be employed to quantify TTD in its pure form and to examine pharmaceutical tablets for the purposes of verifying uniform content. Additionally, it was utilized for the evaluation of TTD concentrations in spiked human plasma.

Novel spectrofluorometric approach for assessing vilazodone by blocking photoinduced electron transfer: analytical performance, and greenness-blueness evaluation.

In this paper, vilazodone (VLD), a serotonin modulator prescribed for major depressive disorder, was investigated using a rapid, highly sensitive, and eco-friendly spectrofluorometric approach. The native fluorescence of VLD, originating from its indole moiety, exhibited an emission peak at 486 nm upon excitation at 241 nm. However, the presence of a piperazinyl nitrogen atom in the VLD structure, acting as an electron donor, significantly diminished the fluorescence intensity through photoinduced electron transfer (PET) to the indole ring. However, by protonating this nitrogen atom using 0.02 M Teorell-Stenhagen buffer (pH 3.5), inhibition of the PET process effectively blocked electron transfer, restoring the fluorescent properties of the drug. Further, an enhancement in the fluorescence was achieved by employing methanol as the solvent, resulting in a 1.5-fold increase. The combined use of PET blockage and methanol enabled the detection of VLD at levels as low as 0.78 ng mL-1. Calibration analysis demonstrated linearity within the range 5-400 ng mL-1, exhibiting a correlation coefficient of 0.9998 and a limit of quantification of 2.37 ng mL-1. The method obeyed the requirements of International Council on Harmonization (ICH). The proposed approach was applied for the accurate measurement of VLD in pharmaceutical tablets, content uniformity testing based on USP requirements, and determining VLD concentration in spiked human plasma. Moreover, the environmental impact, in addition to practical effectiveness, of the proposed approach was evaluated using different metrics.

Development of a green synchronous spectrofluorimetric technique for simultaneous determination of Montelukast sodium and Bilastine in pharmaceutical formulations.

For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50-2000 ng mL-1 for Montelukast sodium and 50-1000 ng mL-1 for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL-1, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL-1, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.

Sensitive spectrofluorimetric determination of the prokinetic drug prucalopride succinate based on supramolecular aggregation approach with evaluation of method greenness: application to content uniformity test.

The prokinetic drug, prucalopride (PCP) succinate, was determined using a new spectrofluorimetric approach with a highly sensitive, rapid, and simple procedure. The method exploited the enhancement of the inherent native fluorescence of PCP by micellar aggregation with sodium lauryl sulfate (SLS) as an anionic surfactant. Different factors that could affect the fluorescence intensity were carefully studied in order to achieve the maximal fluorescence signal. Measurement of the enhanced fluorescence was done at 354 nm after the excitation at 276 nm. The fluorescence intensity-concentration plot was rectilinear in the concentration range of 50-600 ng/ml with detection and quantitation limits of 13.9 and 42.1 ng/ml, respectively. The method underwent validation according to the International Council for Harmonisation criteria in order to assess its analytical performance, and promising results were achieved that proved the validity and reliability of the method. Furthermore, the method was employed effectively for the analysis of the cited drug in commercial pharmaceutical tablets.

Utilization of erythrosine B in spectrofluorimetric quenching analysis of amlodipine and perindopril in pharmaceutical and biological matrices.

A spectrofluorimetric approach that is sensitive, simple, validated, and cost-effective has been proposed for the estimation of amlodipine (AML) and perindopril (PER) in their bulk powders, pharmaceutical formulations, and spiked human plasma. The recommended approach utilized the quantitative quenching effect of the two cited drugs on the fluorescence intensity of erythrosine B, as a result of complex binary reactions among each drug with erythrosine B at pH 3.5 (Teorell and Stenhagen buffer). The quenching of erythrosine B fluorescence was recorded at 554 nm after excitation at 527 nm. The calibration curve was detected in the range 0.25-3.0 µg ml-1 , with a correlation coefficient of 0.9996 for AML, and 0.1-1.5 µg ml-1 , with a correlation coefficient of 0.9996 for PER. The established spectrofluorimetric approach was validated for the estimation of the cited drugs with high sensitivity regarding International Council on Harmonization guidelines. Therefore, the established approach could be utilized for quality control of the cited drugs in their pharmaceutical formulations.

New validated spectrofluorimetric protocol for colistin assay through condensation with 2,2-dihydroxyindan-1,3-dione: application to content uniformity testing.

A new, cost-effective and sensitive spectroscopic assay for the quantification of Colistin Sulfate (CS) and its prodrug colistimethate sodium (CMS) has been developed and validated. The validated technique depends on the condensation of the studied drug with 2,2-dihydroxyindan-1,3-dione (ninhydrin) and phenylacetaldehyde using Teorell and Stenhagen buffer (pH = 6) to yield a fluorescent product that is estimated at emission wavelength (λ em = 474 nm) after excitation wavelength (λ ex = 390 nm). The reaction's affecting factors were carefully studied and adjusted accurately. Over the following range (0.4-2.4 µg mL-1), the produced calibration plot looked rectilinear, and the estimated limits of detection and quantification (LOD and LOQ) were 0.051 & 0.154 µg mL-1 respectively. The recommended approach was utilized to evaluate market products containing the investigated drug. Moreover, content uniformity testing was employed as a new procedure not found in the previously reported fluorimetric technique.

Green innovative fluorescence approach for the feasible and reliable assay of thiol-containing drugs; captopril as a model.

In the present study, a novel spectrofluorimetric approach was designed for the analysis of captopril as a thiol-containing compound. The approach is based on the formation of a ternary fluorescent compound between the target thiol compound, ortho-phthaldehyde, and a suitable primary amine-containing compound. The produced 1-thio-alkyl-isoindole derivative exhibited very high emission activity in a faintly alkaline aqueous solution that could be monitored at 448 nm (excitation at 334 nm). 2-Amino-6-methyl-6-hydroxy-heptane was selected as the primary amine candidate that gave the high fluorescence intensity with the stability of the formed product. At the optimal experimental condition, the intensity of fluorescence of the formed product was linearly related to the concentration of captopril in 20-450 ng mL-1 range. Commercial pharmaceutical tablets were analyzed, and the obtained results agreed with those of the published method regarding precision and accuracy. The mechanism of the reaction was discussed. In addition, the greenness of the approach was rated following eco-scale criteria.

Salvage parenteral antibiotics for multidrug-resistant (MDR) Gram-negative bacteria; a fluorescamine-based technique for ultrasensitive spectrofluorimetric measurement of Polymyxins; human plasma application.

Polymyxins (PMS), namely Colistin (CS) and polymyxin B (poly B), are antimicrobial drugs that have been recently used to treat multiresistant Gram-negative bacteria infections and their resurgence, owing to a lack of new antibiotics. A speedy, simple, and ultrasensitive spectrofluorimetric screening of PMS in pharmaceutical formulations and biological fluids was urgently required from this point forwards. A reaction between fluorescamine and the aliphatic amino moiety found in both drugs was performed in a slightly alkaline borate buffer (pH 8.5) resulted in highly fluorescent products measured at λem 460 (after λex 390.5 nm). Linear calibration curves were constructed over the concentration range 70-1800 ng ml-1 and 100 to 1400 ng ml-1 , with slope values of 0.273 and 0.286, correlation coefficients of 0.9998 and 0.9997, and determination coefficient of 0.9997 and 0.9994 for poly B and CS, respectively. The ultrasensitivity of the proposed method was demonstrated by the very low limit of quantification values of 67.56 ng ml-1 and 94.89 ng ml-1 for poly B and CS, respectively. The cited drugs were successfully determined in their intravenous market preparations by the prescribed method. Moreover, due to the high sensitivity, the suggested method was used to assay the investigated drugs in biological fluids.

The first spectrofluorimetric approach for quantification of colistin sulfate and its prodrug colistimethate sodium in pharmaceutical dosage form and human plasma.

A new, accurate, nonextractive, and sensitive fluorimetric approach was proposed and validated for the first time estimation of colistin sulfate and its inactive prodrug colistimethate sodium in its bulk form, pharmaceutical formulations, and human plasma. The approach relied on condensation between acetylacetone/formaldehyde and the primary amino moiety of nonfluorescent colistin in Teorell and Stenhagen buffer (pH 2.8) by the Hantzsch reaction to form a highly fluorescent dihydropyridine derivative. The fluorescent product was measured at 460 nm (λex  = 402 nm). A plot of relative fluorescence intensity (RFI) versus concentration was rectilinear over the range 200-4000 ng ml-1 with excellent correlation (r) and determination (r2 ) coefficients of 0.9999 and 0.9998, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) were 40.91 and 123.99 ng ml-1 , respectively. The present procedure was useful for determination of colistin sulfate either in powder form for suspension or in its parenteral prodrug colistimethate sodium in vial formulation. The investigated approach was applied for in vitro quantification of this drug in spiked human plasma, with a per cent mean recovery of 98.24 ± 1.34. The proposed method is reliable, selective, and does not require tedious sample pretreatment steps, expensive instrumentation, or harmful reagents, all of which make it ideally suited for use in quality control laboratories.

Development of a novel LC-MS/MS method for detection and quantification of tramadol hydrochloride in presence of some mislabeled drugs: Application to counterfeit study.

Counterfeiting of pharmaceuticals has become a serious problem all over the world, particularly in developing countries. In the present work, a highly sensitive LC-MS/MS method was developed for simultaneous determination of tramadol hydrochloride in the presence of some suspected mislabeled drugs such as alprazolam, diazepam, chlorpheniramine maleate, diphenylhydramine and paracetamol. The prepared samples were analyzed on an API 4000 mass spectrometer using an Eclipse C18 column (3.5 µm, 4.6 × 100 mm). The mobile phase consisting of 0.01% formic acid, acetonitrile and methanol (60:20:20 v/v/v) was pumped with an isocratic elution at a flow rate of 0.7 mL min-1 . The detection was achieved on a triple quadruple tandem mass spectrometer in multiple reaction monitoring mode. The proposed method was successfully validated according to International Conference on Harmonization guidelines with respect to accuracy, precision, linearity, limit of detection and limit of quantitation. The calibration linear range for tramadol hydrochloride, alprazolam, diazepam, chlorpheniramine maleate, diphenylhydramine and paracetamol was 5-500 ng mL-1 . The results revealed that the applied method is promising for the differentiation of genuine tramadol tablets from counterfeit ones without prior separation.

Development and Validation of a Versatile UPLC-PDA Method for Simultaneous Determination of Paracetamol, Tizanidine, Aceclofenac, and Nimesulide in Their New Combinations.

A simple, rapid, and validated UPLC method was developed for the simultaneous quantitation of paracetamol (PAR), tizanidine (TIZ), aceclofenac (ACF), and nimesulide (NIM) either in pure forms or in their different tablet dosage forms. Chromatographic separation was attained on an ACQUITY UPLC™ BEH C18 column (100 mm × 2.1 mm, 1.7 µm) with a mobile phase consisting of 20 mM phosphate buffer (pH 7.0) : acetonitrile in the proportion (60 : 40 v/v) isocratically pumped at a flow rate of 1.25 mL·min-1, and detection was monitored at 305 nm. All analytes were separated simultaneously at a retention time (tr) of 1.42, 2.31, 3.63, and 5.62 min for PAR, TIZ, ACF, and NIM, respectively, with a total run time less than 6.0 min. The proposed method was validated according to ICH guidelines with respect to accuracy, precision, linearity, limit of detection, limit of quantitation, and robustness. Linearity was obtained over a concentration range of 81.25-487.5, 0.5-3.5, 25-150, and 25-150 µg·mL-1 for PAR, TIZ, ACF, and NIM, respectively. The development method can be successfully employed in QC laboratories for the routine analysis of the investigated drugs in their new combination.

Switch on fluorescence probe for the selective determination of lisinopril in pharmaceutical formulations: application to content uniformity testing.

Lisinopril, an ACE inhibitor, was selectively determined in pharmaceutical products using spectrofluorimetry. The method was based on the switch on fluorescamine fluorescence as a result of its interaction with the primary amino group of the drug in the presence of aqueous borate buffer (pH 9.5). The fluorescence emission was measured at 475 nm after excitation at 390 nm. The fluorescent product was suggested to be a diaryl pyrrolone cation which has a coplanar structure. Different experimental conditions affecting the reaction were optimized to give the maximum sensitivity. The fluorescence intensity was linear with the drug concentration in the range of 0.55-4.5 µg mL-1. The method was validated according to ICH guidelines and the result was acceptable. The calculated limits of detection and quantitation were 0.182 and 0.55 µg mL-1, respectively. The commercially available dosage forms containing lisinopril alone or in combination with hydrochlorothiazide were effectively analyzed by the proposed method. The obtained results were in agreement with those of the reported method in respect to accuracy and precession. Moreover, the suggested method was employed to determine the content uniformity testing of the investigated dosage forms.

Novel kinetic spectrophotometric method for estimation of certain biologically active phenolic sympathomimetic drugs in their bulk powders and different pharmaceutical formulations.

A simple, selective and sensitive kinetic spectrophotometric method was described for estimation of four phenolic sympathomimetic drugs namely; terbutaline sulfate, fenoterol hydrobromide, isoxsuprine hydrochloride and etilefrine hydrochloride. This method is depended on the oxidation of the phenolic drugs with Folin-Ciocalteu reagent in presence of sodium carbonate. The rate of color development at 747-760nm was measured spectrophotometrically. The experimental parameters controlling the color development were fully studied and optimized. The reaction mechanism for color development was proposed. The calibration graphs for both the initial rate and fixed time methods were constructed, where linear correlations were found in the general concentration ranges of 3.65×10-6-2.19×10-5molL-1 and 2-24.0µgmL-1 with correlation coefficients in the following range 0.9992-0.9999, 0.9991-0.9998 respectively. The limits of detection and quantitation for the initial rate and fixed time methods were found to be in general concentration range 0.109-0.273, 0.363-0.910 and 0.210-0.483, 0.700-1.611µgmL-1 respectively. The developed method was validated according to ICH and USP 30 -NF 25 guidelines. The suggested method was successfully implemented to the estimation of these drugs in their commercial pharmaceutical formulations and the recovery percentages obtained were ranged from 97.63%±1.37 to 100.17%±0.95 and 97.29%±0.74 to 100.14±0.81 for initial rate and fixed time methods respectively. The data obtained from the analysis of dosage forms were compared with those obtained by reported methods. Statistical analysis of these results indicated no significant variation in the accuracy and precision of both the proposed and reported methods.

An innovative validated spectrofluorimetric method for determination of Lisinopril in presence of hydrochlorothiazide; application to content uniformity testing.

A new sensitive and discriminating spectrofluorimetric method has been developed and validated for determination of Lisinopril, one of the angiotensin converting enzyme inhibitors, in its pure bulk form and pharmaceutical tablets. The reaction of Lisinopril with ethylacetoacetate and formaldehyde in acidic buffered medium (pH3.8) has yielded a pale yellow product that exhibited a high fluorescence measured at 438nm after excitation at 350nm. All the experimental parameters affecting the formation and stability of the produced fluorophore were carefully investigated and optimized to give the maximum sensitivity. The fluorescence intensity was directly proportional to the drug concentration in the range of 0.5-4.5µg/mL with a limit of detection equal to 0.16µg/mL. The method was successfully applied in the analysis of the commercially available pharmaceutical tablets containing the single drug or its binary mixtures with Hydrochlorothiazide. Furthermore, the developed procedure was adapted for studying the content uniformity test of some dosage forms containing the cited drug.

Selective spectrofluorimetric method for determination of Lisinopril in pharmaceutical preparations and in presence of hydrochlorothiazide: Application to content uniformity testing.

A novel sensitive and cost-effective spectrofluorimetric method has been developed and validated for determination of lisinopril (an angiotensin converting enzyme inhibitor) in its pure form and pharmaceutical preparations. The method is based on the reaction of the drug with ninhydrin and phenylacetaldehyde in buffered medium (pH 7.0) to form a highly fluorescent product measured at 460 nm after excitation at 390 nm. Different experimental parameters were optimized and calibration curve was constructed. The fluorescence-concentration relationship was linear in the range of 0.15-4.0 µg mL-1 . The calculated Limit of detection (LOD) and Limit of quantitation (LOQ) were 0.04 and 0.12 µg mL-1 , respectively. The method was successfully applied for the analysis of pharmaceutical preparations containing the studied drug either alone or co-formulated with hydrochlorothiazide. The obtained results were in agreement with those of the reported method in respect to accuracy and precession. Moreover, the method was applied content uniformity testing according to United States Pharmacopeia (USP) guidelines.

Spectrofluorimetric determination of certain adrenergic agonist drugs in their pure forms and pharmaceutical formulations: Content uniformity test application.

A new, simple, sensitive and rapid spectrofluorimetric method has been developed for determination of certain adrenergic agonists such as isoxsuprine hydrochloride, ritodrine hydrochloride and etilefrine hydrochloride in their pure forms and pharmaceutical dosage forms. The method depends on micellar enhancement of the native fluorescence of investigated drugs by using 2% w/v sodium dodecyl sulfate (SDS) as an anionic surfactant. The enhanced fluorescence intensity of investigated drugs was measured at 305 nm after excitation at 278 nm. The interaction of studied drugs with SDS was studied, and the enhanced fluorescence intensity was exploited to develop an assay method for the determination of investigated drugs. The relative fluorescence intensity-concentration plots were rectilinear over the range 0.15-3.00 µg ml-1 , with low quantification limits of 0.132, 0.123 and 0.118 µg mL-1 for isoxsuprine, ritodrine and etilefrine, respectively. The proposed method was successfully applied for determination of studied drugs in their pharmaceutical formulations. Moreover, the high sensitivity of the proposed method allows performing the content uniformity testing of the studied drugs in their tablets by using the official United States Pharmacopeia (USP) guidelines. Statistical comparisons of the results with those of the reported methods revealed excellent agreement and indicated no significant difference in accuracy and precision.