Development of a Diamond Nanoparticles-based Nanosensor for Detection and Determination of Antiviral Drug Favipiravir

This study developed a nanosensor for the detection and determination of favipiravir, a presumed drug that has potential therapeutic efficacy in treating COVID-19 patients, from tablets and serum samples. This nanosensor was obtained by adding the optimum amount of diamond nanoparticles into carbon paste. For the determination of favipiravir adsorptive stripping differential pulse (AdSDPV) and adsorptive stripping square wave voltammetry (AdSSWV) were used. Limit of detection values were found as 4.83×10⁻⁹ M and 2.44×10⁻⁷ M for bulk and 5.18×10⁻⁸ M and 4.38×10⁻⁸ M for serum samples using AdSDPV and AdSSWV, respectively. Recovery studies made of the tablet and serum produced satisfactory results.     

A Validated HPLC Method with Fluorescence Detection for the Determination of Droperidol in Pharmaceutical Tablets,Human Serum,and Human Milk

A sensitive and simple HPLC method with fluorimetric detection has been developed for determination of droperidol in pharmaceutical tablets, human serum, and human milk. Chromatography was performed on a 100 mm × 3 mm i.d. C₁₈ column with methanol–water, 30:70 (v/v), pH 3.5, as mobile phase at a flow-rate of 0.8 mL min⁻¹. The injection volume was 5 μL and detection was by monitoring emission at 324 nm after excitation at 283 nm. Droperidol and p-hydroxybenzoic acid (internal standard) eluted after 5.3 and 6.1 min, respectively. The method was validated over the concentration range 1.14 × 10⁻⁷ to 9.12 × 10⁻⁶ M. Selectivity was good and the limits of detection and quantitation of the method were approximately 3.54 × 10⁻⁸ and 1.07 × 10⁻⁷ M, respectively, corresponding to 13 and 40 ng mL⁻¹. The applicability of the method to determination of droperidol in pharmaceuticals, human serum, and human milk was demonstrated.

     

Detection of Agmatine and Octopamine in Rat Brain and Human Plasma by Microchip Electrophoresis

A microchip electrophoresis method with laser induced fluorescence detection was developed for the detection of agmatine (Agm) and octopamine (Oct). The fluorescent derivatization reagent, fluorescein isothiocyanate was used for precolumn derivatization of Agm and Oct. The sodium dodecyl sulfate (SDS) micelles was employed as pseudostationary phase for the separation of Agm and Oct with other endogenous compounds exist in biological samples. Some parameters including buffer concentration, buffer pH, SDS concentration and separation voltage were investigated in detail. Under the optimum conditions, the separation and determination of Agm and Oct was performed within 40 s. The calibration curves were linear for both Agm and Oct over the concentration range of 1.0 × 10⁻⁷ to 4.0 × 10⁻⁵ M and 1.5 × 10⁻⁷ to 4.5 × 10⁻⁵ M, respectively. The detection limits of Agm and Oct (S/N = 3) are 5.0 × 10⁻⁸ and 8.0 × 10⁻⁸ M, respectively. These values make the method very suitable for the determination of Agm and Oct in rat brain tissue and human plasma as demonstrated in this paper.

     

Electrochemical Analysis of Antipsychotic Drug Quetiapine Fumarate Using Multi-walled Carbon Nanotube Modified Glassy Carbon Electrode

Electrochemical properties of quetiapine fumarate were examined on the anodic direction with multi-walled carbon nanotube modified glassy carbon electrode using voltammetric methods. The ratio of multi-walled carbon nanotube has been optimized using its various concentrations. The oxidation process was found to be irreversible, and adsorption controlled. The linear ranges were determined as 4×10⁻⁹–2×10⁻⁶ M for differential pulse stripping voltammetry and 2×10⁻⁹–2×10⁻⁶ M for square-wave stripping voltammetry with detection limits of 8.07×10⁻¹⁰ and 2.71×10⁻¹⁰ M, respectively. The methods were validated and successfully applied for the analysis of quetiapine fumarate tablets. The groups responsible for the oxidation reaction of quetiapine fumarate were investigated with model substances.     

Determination of Sotalol in Tablets and Serum by CZE

A validated capillary zone electrophoretic method for analysis of sotalol is described. Analysis was performed in a fused-silica capillary with 20 mM phosphate buffer (pH 4.20) containing 10% (v/v) acetonitrile as background electrolyte. The applied potential was +20 kV, the injection time 0.08 min, signal detection was at 200 nm, and 3,4-dihydoxybenzylamine was used as internal standard. The method was validated over the concentration range 1.98 × 10⁻⁵ to 9.90 × 10⁻⁵ M; repeatability was good and there was no interference. Highly satisfactory results were obtained from analysis of tablets and serum, indicating the method is specific, accurate, and precise, and suitable for routine analysis of sotalol in pharmaceutical tablets and in pharmacokinetic studies.

     

A Validated Voltammetric Procedure for Quantification of the Antifungal Drug Griseofulvin in Bulk Form,Tablets, and Biological Fluids at a Mercury Electrode

Abstract

Griseofulvin is an antifungal antibiotic used to treat various pathogenic mycotic diseases. The voltammetric behavior of griseofulvin at a hanging mercury drop electrode in Britton‐Robinson buffers of pH 2–11.5 was studied and discussed. A fully validated sensitive square‐wave adsorptive cathodic stripping voltammetric procedure was described for direct determination of bulk griseofulvin substance. The procedure was based on the reduction of the >C?O double bond of griseofulvin molecule following its preconcentration onto a hanging mercury drop electrode in a Britton‐Robinson buffer of pH 10. Limits of detection (LOD) and quantitation (LOQ) of 5.8×10^?10 M and 1.93×10^?9 M bulk griseofulvin were achieved, respectively. The proposed stripping voltammetric procedure was successfully applied to assay griseofulvin in tablets and in spiked human serum and urine samples. LOD of 8.65×10^?10 M and 6.6×10^?9 M and LOQ of 2.88×10^?9 M and 2.2×10^?8 M griseofulvin in spiked human serum and urine samples, respectively, were achieved.     

Electrochemical determination of prolintane in pharmaceutical formulations and in human urine

The oxidative behavior of 1-[1-(phenylmethyl)butyl]pyrrolidine, prolintane, was studied at a glassy carbon electrode using linear-sweep and differential-pulse voltammetry. The oxidation process was shown to be irreversible using 0.04 M Britton–Robinson buffer and was diffusion-adsorption controlled. Two voltammetric methods were developed for the determination of prolintane using different techniques: linear-sweep and differential-pulse voltammetry. The peak current varied linearly with prolintane concentrations in the range of 1.0 × 10⁻⁵ −2.5 × 10⁻⁴ M, with a detection limit of 8.5 × 10⁻⁶ and 4.0 × 10⁻⁶ M, and with relative standard deviations of 2.1 % and 3.1 %, respectively. The methods were applied to commercial preparations, giving relative errors less than 3.1 % and relative standard deviations lower than 4.8 % (n = 10). Determination of prolintane (down to the 8.5 × 10⁻⁸ M level) can be performed by using a preconcentration step prior to the determination by differential-pulse voltammetry in 0.04 M Britton–Robinson buffer (pH 8.0) with preconcentration potential of 0.0 V. The detection limit was found to be 6.2 × 10⁻⁸ M (4 min preconcentration) and the relative standard deviation for 2.5 × 10⁻⁷ M prolintane (n = 5) was 4.6 %. Applicability to human urine analysis is illustrated (recovery 98 ± 2 %). Standard additions method can be used to determine prolintane in real samples of urine.     

Stability-Indicating LC Method for the Determination of Lacidipine in Tablets. Application to Degradation Kinetics and Content Uniformity Testing

A simple, stability-indicating, reversed-phase liquid chromatographic method was developed for the determination of lacidipine in the presence of its degradation products. The analysis was carried out using a 150 mm × 4.6 mm i.d., 5 μm particle size Nucleodur MN-C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer (70:30) at pH = 5.0 was pumped at a flow rate of 1 mL min⁻¹ with UV-detection at 254 nm. The method showed good linearity in the range of 0.06–15 μg mL⁻¹ with a limit of detection (S/N = 3) of 0.016 μg mL⁻¹ (3.5 × 10⁻⁸ M). The suggested method was successfully applied for the analysis of lacidipine in bulk and in commercial tablets with average recoveries of 100.19 ± 0.81% and 100.05 ± 0.69%, respectively. The results were favorably compared to those obtained by a reference method. The suggested method was utilized to investigate the kinetics of alkaline, acidic, peroxide and photo-induced degradation of the drug. The apparent first-order rate constant, half-life times and activation energies of the degradation process were calculated. The pH profile curve was derived. The proposed method was successfully applied to the content uniformity testing of tablets.

     

Anodic Voltammetric Behavior and Determination of Antihistaminic Agent: Fexofenadine HCl

Abstract

A voltammetric study of the oxidation of fexofenadine HCl (FEXO) has been carried out at the glassy carbon electrode. The electrochemical oxidation of FEXO was investigated by cyclic, linear sweep, differential pulse (DPV), and square wave (SWV) voltammetry using glassy carbon electrode. The oxidation of FEXO was irreversible and exhibited diffusion‐controlled process depending on pH. The dependence of intensities of currents and potentials on pH, concentration, scan rate, nature of the buffer was investigated. Different parameters were tested to optimize the conditions for the determination of FEXO. For analytical purposes, a very well resolved diffusion‐controlled voltammetric peak was obtained in Britton‐Robinson buffer at pH 7.0 with 20% constant amount of methanol for DPV and SWV techniques. The linear response was obtained in supporting electrolyte in the ranges of 1.0×10^?6–2.0×10^?4 M with a detection limit of 6.6×10^?9 M and 5.76×10^?8 M and in serum samples in the ranges of 2.0×10^?6–1.0×10^?4 M with a detection limit of 8.08×10^?8 M and 4.97×10^?8 M for differential pulse and square wave voltammetric techniques, respectively. Only square wave voltammetric technique can be applied to the urine samples, and the linearity was obtained in the ranges of 2.0×10^?6–1.0×10^?4 M with a detection limit of 2.00×10^?7 M. Based on this study, simple, rapid, selective and sensitive two voltammetric methods were developed for the determination of FEXO in dosage forms and biological fluids. For the precision and accuracy of the developed methods, recovery studies were used. The standard addition method was used for the recovery studies. No electroactive interferences were found in biological fluids from the endogenous substances and additives present in tablets.     

Electrochemical behaviors and determination of melamine in neutral and acid aqueous media

The electrochemical behaviors of melamine (MEL) were studied at paraffin-impregnated graphite electrode in PBS (pH 7.0) and 0.5 M H₂SO₄. Various methods including UV–vis thin-layer spectroelectrochemistry, infrared spectra (IR) and electrochemicatry have been performed to investigate the characteristics. In 0.1 M PBS (pH 7.0), MEL loses two electrons to form a dication, which couples head-to-head with a neutral molecule of MEL to form a dimer accompanying the production of azocompound, the dimer plays a role of a monomer in the following polymerization. In 0.5 M H₂SO₄, unstable MEL mostly hydrolyzes to form ammeline, ammelide, s-triazine-2,4,6-trion, and tricyanic acid, respectively; The hydrolysis could be accelerated by electrochemical method; Meanwhile, MEL associates tricyanic acid to give a plane molecule cake by hydrogen bonding. The spectra responses of MEL at 205 and 234 nm are linearly increasing in a same concentration range of 1.0 × 10⁻⁷–1.0 × 10⁻⁵ M in 0.5 M H₂SO₄ (determination limit, 1 × 10⁻⁸ and 3 × 10⁻⁸ (3σ)). The proposed method was successfully applied to the determination of MEL in real sample.

     

Determination of Albumin Using the Chemiluminescence of Tb3+/K2S2O8 System

A new chemiluminescence system of Tb³⁺/K₂S₂O₈ was developed for the determination of albumin. Some experimental conditions were examined and optimized. The linear ranges of the calibration curves are 5.0 × 10^?9–5.0 × 10^?6 mol/L for bovine serum albumin, 5.0 × 10^?8–1.0 × 10^?5 mol/L for human serum albumin and 2.5 × 10^?7–1.0 × 10^?5 mol/L for ovalbumin, and the corresponding detection limits are 1.9 × 10^?9 mol/L, 1.5 × 10^?8 mol/L, and 1.5 × 10^?7 mol/L, respectively. The method was applied to the determination of albumin in human serum samples, and the results were in agreement with those obtained by the bromcresol green method. The relative errors for the analytical results were from ?2.0% to 4.3%.     

Analysis of 5-methyltetrahydrofolate in human blood, serum and urine by on-line coupling of capillary isotachophoresis and zone electrophoresis

The predominant circulating folate coenzyme in plasma/serum, 5‐methyltetrahydrofolate (5‐MTHF) was determined in human blood, serum and urine using a method based on the hyphenation of capillary ITP and zone electrophoresis. Measurements were done with a commercially available instrument for capillary isotachophoresis equipped with a column‐switching system. The choice of electrolytes was limited by the instability of 5‐MTHF and volatility of electrolytes for the potential coupling of the instrumentation with MS detector. To get an insight into the separability of individual sample components in an isotachophoretic analysis, we constructed zone existence diagrams for isotachophoretic electrolyte systems having a leading electrolyte composed of acetate and ammonium of pH 4.5 and 7.0, hydrocarbonate and ammonium, pH 7.8, chloride and ammonium, pH 5.6, and chloride and creatinine, pH 5.0, with hydroxide ion as the terminator. For isotachophoretic preseparation, the non‐volatile leading electrolyte with good buffering capacity composed of 1×10⁻² M HCl and 2.5×10⁻² M creatinine, pH 5.0, and terminating electrolyte composed of 1×10⁻² M MES was selected as the most suitable. The optimum BGE for CZE analysis from the standpoint of analyte stability, separability and volatility for MS coupling was 1×10⁻² M acetate with 3.5×10⁻² M ammonium, pH 4.5. Using this combination of electrolytes, LODs reached with optical detection at 220 nm were 1.6×10⁻⁷ M in human blood, 1.1×10⁻⁷ M in human serum and 4.7×10⁻⁶ M in human urine. Estimated content of 5‐MTHF in blood and serum samples of women following oral daily administration of 0.8 mg of folic acid was 1.2×10⁻⁵ and 5.8×10⁻⁶ M, respectively.     

Development and Validation of an RP-HPLC Method for Determination of Valganciclovir in Human Serum and Tablets

This paper describes the validation of an isocratic high-performance liquid chromatographic method for the assay of valganciclovir in raw materials, tablets and human serum samples. Valganciclovir and fluvastatin (internal standard) were well separated using a reversed phase column and a mobile phase consisting of a mixture of acetonitrile:methanol:KH₂PO₄ (0.02 M) (40:20:40; v/v/v) (at pH 5.0). The mobile phase was pumped at 1.0 mL min⁻¹ flow rate and valganciclovir was detected by diode-array detection at 255 nm. The retention times for valganciclovir and fluvastatin were 3.41 and 5.60 min, respectively. A linear response (r > 0.999) was observed in the range of 10–30,000 ng mL⁻¹ in mobile phase and serum. The limit of detection and limit of quantification were found as 2.95 and 9.82 ng mL⁻¹ in mobile phase and 1.73 and 5.77 ng mL⁻¹ in human serum samples, respectively. Validation parameters as precision, accuracy, selectivity, reproducibility and system suitability tests were also determined. The method can be used for valganciclovir assay of tablets and human serum samples as the method separates valganciclovir from tablet excipients and endogenous substances.

     

GC Determination of Famotidine,Ranitidine, Cimetidine,and Metformin in Pharmaceutical Preparations and Serum Using Methylglyoxal as Derivatizing Reagent

A capillary gas chromatography (GC) procedure has been developed for the determination of four pharmaceutical preparations (famotidine, ranitidine, cimetidine, and metformin) after precolumn derivatization with methylglyoxal (MGo). GC was carried out using an HP-5 column (30 m × 0.32 mm id) at an initial column temperature of 90 °C for 2 min, followed by heating rate of 25 °C min⁻¹ up to 265 °C. Nitrogen flow rate was 2.5 mL min⁻¹ with split ratio 10:1. A linear calibration curve was obtained within 50–1,000 ng mL⁻¹ and the limit of detection (LOD) was within 17–25 ng mL⁻¹. The derivatization, GC elution, and separation were repeatable in terms of retention time and peak height/peak area with relative standard deviation within ±4.6 %. The procedure was applied to the determination of the drugs in pharmaceutical preparations and the sera of volunteers who were given oral doses of the drugs. The results of the analysis agreed with the labeled values of the pharmaceutical preparations and were 147–4,903 ng mL⁻¹ in serum with an RSD within 1.0–4.2 %, after ingestion of a single dose of 40–500 mg of active ingredient in a tablet.

     

Simultaneous Determination of Procaspase Activating Compound 1 and Permeability Markers in Intestinal Perfusion Samples and Application to a Rat Intestinal Absorption Study

A sensitive and simple HPLC method for simultaneous determination of PAC-1 (first procaspase-activating compound), phenol red, and permeability markers (carbamazepine and furosemide) in perfusion samples was developed and validated to assess intestinal absorption of PAC-1 using single-pass intestinal perfusion technique (SPIP) in rats. The chromatographic separation was carried out on a Kromasil C₁₈ column (150 mm × 4.6 mm, 5 μm) with acetonitrile–methanol–30 mmol L⁻¹ phosphate buffer (pH 3.0, 25:10:65, v/v/v) as mobile phase at a flow rate of 1.0 mL min⁻¹, and the wavelength of the UV detector was set at 281 nm. The calibration curves were linear in the ranges of 2.40–48.0 μg mL⁻¹ for PAC-1; 3.60–72.0 μg mL⁻¹ for carbamazepine; 3.20–64.0 μg mL⁻¹ for furosemide, and 4.80–96.0 μg mL⁻¹ for phenol red (r > 0.999). Both the intra- and inter-day precisions (RSD%) of all analytes were less than 6.8 % at three concentration levels, while accuracy ranged from 95.4 to 104.5 %. Data obtained in all method validation studies indicated that the method was suitable for the intended purpose. The effective permeability values (P _eff) considering water flux with the help of non-permeable marker phenol red was calculated to be 0.42 × 10⁻⁴, 0.62 × 10⁻⁴, 0.32 × 10⁻⁴ cm s⁻¹ for PAC-1; 0.72 × 10⁻⁴, 0.77 × 10⁻⁴, 0.52 × 10⁻⁴ cm s⁻¹ for carbamazepine; 0.20 × 10⁻⁴, 0.16 × 10⁻⁴, 0.12 × 10⁻⁴ cm s⁻¹ for furosemide in duodenum, jejunum and ileum, respectively. The P _eff value can be increased by co-perfusion with verapamil, indicating that absorption of PAC-1 is efficiently transported by P-glycoprotein (P-gp) in the gut wall.

     

Division Electrosynthesis of Palladium Nanomaterials with Copper–Graphene as Sacrificial Templates and Its Application for Hydrazine Sensing

One‐pot electrodeposited copper‐graphene (Cu‐GE ) nanocomposite acting as sacrificial template for the division electrosynthesis of palladium nanoparticles (PdNPs ) on pyrolytic graphite electrode (PGE ) was synthesized. The designed PdNPs‐GE nanocomposite was evaluated as a new material for highly sensitive determination of hydrazine (N₂H₄ ). Scanning electron microscopy revealed that the PdNP‐GE ‐modified PGE had uniform morphology. The results of energy‐dispersive X‐ray spectrograms confirmed the ingredients of the division electrosynthesis process. Electrochemical experiments were performed to characterize the sensing properties of PdNPs‐GE toward the electrocatalytic oxidation of N₂H₄ at 0.20 V in sodium phosphate buffered saline (0.1 M pH 7.0). The sensor showed fast response (<3 s), high sensitivity [398 (1 × 10⁻⁶ A) (1 × 10⁻³ M)⁻¹], and broad linearity in the range 2.5 × 10⁻⁸–2.7 × 10⁻⁴ M with a relatively low detection limit of 1.0 × 10⁻⁸ M (S/N = 3).     

Structure and conductivity of AOT solutions in n-hexadecane-chloroform mixtures

The structure and conductivity of AOT (sodium bis(2-ethylhexyl) sulfosuccinate) solutions (2.5 × 10⁻⁴–2.5 × 10⁻¹ M) in n-hexadecane-chloroform mixture at the chloroform concentration from 50 to 100 vol% were studied. The diffusion ordered spectroscopy NMR study revealed that in the indicated range, the observed hydrodynamic diameter of micelles depends only on the AOT concentration and does not depend on the chloroform content. Molar fractions of free AOT molecules and those aggregated into micelles were calculated using the Lindman's law: at concentrations above 2.5 × 10⁻¹ М, the solutions contain mostly the micelles, whereas at concentrations below 2.5 × 10⁻⁴ M, the solutions contain AOT molecules. The transition region contains both the AOT molecules and the micelles. Conductivity measurements were used to determine free charge carriers in the bulk of solutions and their contributions to conductivity.     

Praseodymium Doped Dysprosium Oxide-carbon Nanofibers Based Voltammetric Platform for the Simultaneous Determination of Sunset Yellow and Tartrazine

A platform based on praseodymium doped dysprosium oxide-carbon nanofibers modified electrode was constructed for the simultaneous determination of SY and TAR. SEM, EDX and XRD techniques were utilized for characterizing the proposed material. The voltammetric behaviour and properties of SY and TAR were gradually improved at materials in order from CNFs to Dy₂O₃−CNFs and Pr₆O₁₁@Dy₂O₃−CNFs. The working range was found to be 1.0×10⁻⁹–3.5×10⁻⁸ M and 1.5×10⁻⁹–4.0×10⁻⁸ M for SY and TAR, respectively. The value of LOD was 3.12×10⁻¹⁰ M and 5.35×10⁻¹⁰ M for SY and TAR, respectively. The platform (Pr₆O₁₁@Dy₂O₃−CNFs/GCE) was successfully applied to the electroanalysis of samples.     

Electrochemical Sensing Platform Based on Graphene Oxide-chitosan for Simultaneous Determination of some Antihypertensive Drugs

The development of selective and simple methods for the determination of different analytes is of great interest. This is the first time to show the applicability of graphene oxide-chitosan (GO-CS) nanocomposite for designing an electrochemical nanosensor for determination of Amlodipine, Valsartan, and Hydrochlorothiazide, simultaneously. Differential pulse voltammetrics current of AML, HCT, and VAL increased linearly in the ranges of 0.1–110, 0.1–110, and 1–230 μM with LOD of 5.5×10⁻², 3.5×10⁻² and 8.6×10⁻² μM, respectively. Finally, GO-CS/GCE was used for the detection of these drugs in commercial tablets and compared with the reference method (HPLC).     

Determination of Flavonoid Markers in Honey with SPE and LC using Experimental Design

Determination of flavonoid markers quercetin, hesperetin, and chrysin, found in north Iranian citrus honey samples, was carried out by solid phase extraction (SPE) and isocratic liquid chromatographic separation using central composite design. Optimum conditions for SPE were achieved using 10 mL methanol/water (13:87, v/v, pH = 7) as the washing solvent and 4 mL methanol for elution. Good clean-up and high recovery >90% were observed for all analytes. The use of water/ACN/THF/AcOH (54:36:5:5, v/v) was found to serve as the optimum mobile phase composition and allowed for the separation of analytes from endogenous compounds present in honey. SPE parameters, such as maximum loading capacity and breakthrough volume, were also determined for each analyte. Limit of detection, linear range, recovery, repeatability of retention times, and peak heights were 3.11 × 10⁻⁸–4.44 × 10⁻⁸ g g⁻¹, 0.50–50.0 μg mL⁻¹ (R ² > 0.99), 90.7–96.9%, 3.0–3.6%, and 1.0–2.6%, respectively. Precision of the overall analytical procedure, estimated by five replicate measurements for quercetin, hesperetin and chrysin in citrus honey, as well as the relative standard deviations were 4.3%, 3.8%, and 5.5%, respectively.