Challenge Approach of an Inexpensive Electrochemical Sensor for Rapid Selective Determination of two Non‐classical β‐Lactams in Presence of Different Degradants and Interference Substances

An inexpensive stability−indicating anodic voltammetric method for rapid determination of two non‐classical β ‐lactam antibiotics; Meropenem (MP) and Ertapenem (EP) has been developed and validated. The method was based on the enhancement of voltammetric response at a disposable graphite pencil electrode (GPE). Differential pulse voltammetric (DPV) method was developed for quantification of both drugs in B−R buffer solution (pH 2.0) at GPE. The GPE displayed very good voltammetric behavior with significant enhancement of the peak current compared to glassy carbon electrode (GCE). Stress stability studies were performed using 0.5 M of either HCl or NaOH and H₂O₂. Mass and infrared spectroscopy were used for identification of degradants and their pathways were illustrated. Under optimal conditions, the peak currents showed a linear dependence with drug concentrations. The achieved limits of detection (LOD) were 1.23, 2.07 and 1.50 μM for MP and two waves of EP, respectively. The developed voltammetric method was successfully applied for direct determination of MP and EP in drug substances, pharmaceutical vials and in presence of either their corresponding hydrolytic, oxidative‐degradants or interfering substances with no potential interferences. The differential pulse voltammograms were highly advantageous and applicable in QC laboratories for rapid, selective micro‐determination of MP and EP.     

An Electrochemical Sensor Based on Silver Nanoparticles‐Benzalkonium Chloride for the Voltammetric Determination of Antiviral Drug Tenofovir

A simple voltammetric nanosensor was described for the highly sensitive determination of antiviral drug Tenofovir. The benzalkonium chloride and silver nanoparticles were associated to build a nanosensor on glassy carbon electrode. Surface characterictics were achieved using scanning electron microscopic technique. The voltammetric measurements were performed in pH range between 1.0 and 10.0 using cyclic, adsorptive stripping differential pulse and adsorptive stripping square wave voltammetry. The linear dependence of the peak current on the square root of scan rates and the slope value (0.770) demonstrated that the oxidation of tenofovir is a mix diffusion‐adsorption controlled process in pH 5.70 acetate buffer. The linearity range was found to be 6.0×10⁻⁸–1.0×10⁻⁶ M, and nanosensor displayed an excellent detection limit of 2.39×10⁻⁹ M by square wave adsorptive stripping voltammetry. The developed nanosensor was successfully applied for the determination of Tenofovir in pharmaceutical dosage form. Moreover, the voltammetric oxidation pathway of tenofovir was also investigated at bare glassy carbon electrode comparing with some possible model compounds (Adenine and Adefovir).     

多金属氧酸盐抗病毒药物研究

多金属氧酸盐在抗病毒、抗肿瘤、抗细菌方面的研究取得了重要进展,本文综述了近30年来多金属氧酸盐在抗艾滋病毒(HIV)、疱疹病毒(HSV-1、HSV-2)、流感病毒等方面的研究情况,详细总结了各种类型多金属氧酸盐的抗病毒效果。结合本课题组的研究结果比较分析了多金属氧酸盐的结构及其抗病毒效果的差异。     

Electroanalytical investigation and determination of pefloxacin in pharmaceuticals and serum at boron-doped diamond and glassy carbon electrodes

The anodic behavior and determination of pefloxacin on boron-doped diamond and glassy carbon electrodes were investigated using cyclic, linear sweep, differential pulse and square wave voltammetric techniques. In cyclic voltammetry, pefloxacin shows one main irreversible oxidation peak and additional one irreversible ill-defined wave depending on pH values for both electrodes. The results indicate that the process of pefloxacin is irreversible and diffusion controlled on boron-doped diamond electrode and irreversible but adsorption controlled on glassy carbon electrode. The peak current is found to be linear over the range of concentration 2 × 10⁻⁶ to 2 × 10⁻⁴ M in 0.5 M H₂SO₄ at about +1.20 V (versus Ag/AgCl) for differential pulse and square wave voltammetric technique using boron-doped diamond electrode. The repeatability, reproducibility, precision and accuracy of the methods in all media were investigated. Selectivity, precision and accuracy of the developed methods were also checked by recovery studies. The procedures were successfully applied to the determination of the drug in pharmaceutical dosage forms and humans serum samples with good recovery results. No electroactive interferences from the excipients and endogenous substances were found in the pharmaceutical dosage forms and biological samples, respectively.     

Synthesis and Evaluation of Some Uracil Nucleosides as Promising Anti-Herpes Simplex Virus 1 Agents

Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.     

Fabrication of an Electrochemical Sensor Based on Multiwalled Carbon Nanotubes for Almotriptan

In the present work, the electrochemical behavior of an antimigraine drug, almotriptan malate (ALM), on a multiwalled carbon nanotube (MWCNT) film modified glassy carbon electrode under cyclic voltammetry was described for the first time. A significant enhancement in the oxidation peak current of ALM was noticed at MWCNT‐GCE. This property was exploited to develop a simple, sensitive and time‐saving differential pulse voltammetric method for the determination of ALM in bulk and pharmaceutical samples. A linear relationship was observed between concentration and peak current with a correlation coefficient of 0.9915 in the range of 0.25–37.5 µM ALM.     

Polarographic and Voltammetric Assays of Sulfonamides as α‐Oxo‐γ‐Butyrolactone Arylhydrazones

Abstract

2‐Acetylbutyrolactone was characterized as a novel reagent of analytical potential in polarographic and voltammetric analyses. It forms α‐oxo‐γ‐butyrolactone arylhydrazones through Japp‐Klingemann coupling reaction with primary arylamines. α‐Oxo‐γ‐butyrolactone arylhydrazones possess an electro‐active site (azomethine center) that displays a cathodic activity at the mercury electrode. The protonated azomethine center of α‐oxo‐γ‐butyrolactone arylhydrazones is reduced by 2e/2H⁺ reaction to the hydrazo form. The differential pulse polarographic behavior of α‐oxo‐γ‐butyrolactone arylhydrazones was investigated in aqueous media ranging from pH 2 to 10.5. In aqueous acidic solution, α‐oxo‐γ‐butyrolactone arylhydrazones were shown to adsorb on a hanging mercury drop electrode and to be amenable to determination by adsorptive stripping voltammetry. Procedures for applying the polarographic and voltammetric methods to determination of sulfadiazine and sulfamethoxazole in pharmaceutical preparations have been developed. An analogous study on sulfas‐azo derivatives of ethyl acetoacetate was also considered. Furthermore, the differential pulse voltammetric method was adopted for determination of sulfamethoxazole in spiked plasma and urine samples. The recoveries turned out to be satisfactory, showing relative standard deviations from 2.4 to 4.6%.     

Antiviral Effect of Nonfunctionalized Gold Nanoparticles against Herpes Simplex Virus Type-1 (HSV-1) and Possible Contribution of Near-Field Interaction Mechanism

The antiviral activity of nonfunctionalized gold nanoparticles (AuNPs) against herpes simplex virus type-1 (HSV-1) in vitro was revealed in this study. We found that AuNPs are capable of reducing the cytopathic effect (CPE) of HSV-1 in Vero cells in a dose- and time-dependent manner when used in pretreatment mode. The demonstrated antiviral activity was within the nontoxic concentration range of AuNPs. Interestingly, we noted that nanoparticles with smaller sizes reduced the CPE of HSV-1 more effectively than larger ones. The observed phenomenon can be tentatively explained by the near-field action of nanoparticles at the virus envelope. These results show that AuNPs can be considered as potential candidates for the treatment of HSV-1 infections.     

Simple and rapid determination of clonidine in pharmaceutical samples by voltammetry using a bare glassy carbon electrode

This work presents, for the first time, the voltammetric behavior of clonidine (CLO) drug and its determination, using an unmodified glassy carbon electrode (GCE). CLO exhibited only an irreversible oxidation process on the GCE, with peak potential at +0.85 V in pH 12 (vs Ag/AgCl). CLO oxidation process is pH-dependent and the electrochemical mechanisms on the GCE were proposed in acidic and basic medium. The determination of CLO was optimized in 0.1 mol L⁻¹ phosphate buffer solution at pH 12.0 using differential pulse voltammetry (DPV), which provides a good linear range (0.65 to 106.00 μmol L⁻¹) and low theoretical limit of detection (0.14 μmol L⁻¹) for the quality control of this drug in pharmaceutical samples. In addition, stable responses of CLO at the GCE were obtained in the same day (RSD = 3.4 %; n = 5) and different days (RSD = 2.0 %; n = 3). Moreover, the determination of CLO in a pharmaceutical formulation using the proposed GCE-DPV method presented good accuracy, since the recovery was close to 100 % and the dosing result was in agreement with an official method (HPLC-UV). The proposed method demonstrates a good analytical performance for CLO determination in pharmaceutical samples, providing a faster, simpler and lower-cost alternative for quality control of CLO than other reported methods.     

Novel antiviral fucoidan from sporophyll of Undaria pinnatifida (Mekabu)

Structural characterization and antiviral activities of fucoidan from sporophyll of Undaria pinnatifida (Mekabu) was examined. The fucoidan was composed of fucose and galactose with an approximately ratio of 1.0:1.1. Degree of substitution of sulfate was 0.72 and its apparent molecular weight was 9,000. Methylation analyses showed that fucoidan had various sugar linkages, and revealed that the fucoidan might have complicated structure. This fucoidan showed potent antiviral activities against herpes simplex virus type 1 (HSV-1), HSV-2, and human cytomegalovirus.     

Voltammetric behaviour of antimalarial drug artesunate in solubilized systems

The voltammetric behaviour of artesunate is studied at glassy carbon electrode in different buffer systems using square wave, differential pulse and cyclic voltammetric techniques. The peak current is linear with the drug concentration in the range 4.0-40 μg mL(-1) for serum, plasma and urine. The mean percentage recoveries of the drug, urine, plasma and serum samples are 98.6-100.2%. No electroactive interferences from the excipients and endogenous substance could be observed in the pharmaceutical dosage forms and in biological samples.     

Voltammetric Determination of Oxybutynin Hydrochloride Utilizing Pencil Graphite Electrode Decorated with Gold Nanoparticles

A novel voltammetric method was successfully applied for the determination of an anticholinergic drug, oxybutynin hydrochloride (OXB). The method is concerned with electrooxidation of the drug on the surface of pencil graphite electrode (PGE). In order to enhance the electrode sensitivity and peak current, the electrode was coated with gold nanoparticles (Au-NPs) via electrochemical deposition using cyclic voltammetry from gold salt solution. The surface of Au-NPs modified PGE has been characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. Various experimental variables were studied and optimized to enhance the sensor's response towards OXB. Quantitative determination of the drug was achieved in phosphate buffer pH 7.5 using differential pulse voltammetry by scanning the potential over range of 0.00 to 2.20 V with scan rate of 40 mV s⁻¹. Validation of the method was achieved according to ICH guidelines. The method was found to be linear over concentration range (2.0×10⁻⁷–1.0×10⁻⁶ M). The suggested sensor was efficiently developed for the quantitative determination of OXB in pure form, pharmaceutical dosage form and spiked plasma samples.     

差分脉冲伏安法测定卡托普利

本文基于金电极表面对巯基化合物的吸附作用,提出了一种简便灵敏的测定抗高血压药物卡托普利的新方法.研究了卡托普利在金电极上的伏安响应,优化了差分脉冲伏安法测定卡托普利的实验条件.研究结果表明:在0.217～3.04 mg/L的范围内,卡托普利的氧化峰电流与其浓度呈良好的线性关系,检出限为0.152 mg/L.测定药物中卡...     

Voltammetric Determination of Chlorpheniramine Maleate Based on the Enhancement Effect of Sodium‐dodecyl Sulfate at Carbon Paste Electrode

The voltammetric oxidation and determination of chlorpheniramine maleate (CPM) was studied at a carbon paste electrode (CPE) in the presence of sodium‐dodecyl sulfate (SDS) by cyclic and differential pulse voltammetry. The results indicated that the voltammetric response of chlorpheniramine maleate was markedly increased in the low concentration of SDS, suggesting that SDS exhibits observable enhancement effect to the determination of chlorpheniramine maleate. Under the optimal conditions the peak current was proportional to chlorpheniramine maleate concentration in the range of 8.0×10⁻⁶ to 1.0×10⁻⁴ M with detection limit of 1.7×10⁻⁶ M by differential pulse voltammetry. The proposed method was successfully applied to the determination of chlorpheniramine in pharmaceutical and urine samples.     

Polybenzoin Based Sensor for Determination of 2thiouracil in Biological Fluids and Pharmaceutical Formulations

A carbon paste electrode was modified by electropolymerisation of benzoin using voltammetric technique. A novel polybenzoin modified carbon paste electrode (PB‐CPE) was developed for use as a detector in cyclic voltammetry and differential pulse adsorptive stripping voltammetry for the sensitive determination of 2thiouracil (2TU). The atomic force microscopy was applied to characterize the surface morphology of PB‐CPE. The modified electrode showed excellent electrocatalytic activity for the oxidation of 2TU. The oxidation process was irreversible over the pH range studied and exhibited a diffusion controlled behavior. All experimental parameters have been optimized. The peak current for the stripping of 2TU was found to be linear over the concentration range of 0.2–1.2 µM, with a detection limit of 2.21 nM. The practical application of the PB‐CPE in the determination of 2TU in human biological fluids and pharmaceutical samples were demonstrated that it has high sensitivity and good selectivity.     

Synthesis and antiviral activities of synthetic glutarimide derivatives

A series of novel glutarimide compounds were synthesized and their antiviral activities were evaluated. The compounds displaying the strongest antiviral activities included 5, 6f, 7e and 9 against coxsackievirus B3 (Cox B3), 10 and 6f against influenza virus A (influenza A) and 7a against herpes simplex virus 2 (HSV-2). However, most of the synthetic glutarimides showed comparatively much weaker activity against influenza A, Cox B3 and HSV-2 than the natural glutarimide compounds tested. Based on the results, it seemed likely that a conjugated system at the β-substituted moiety provides stronger antiviral activity.     

Structure-activity relationships in distamycin A analogues: effect of alkyl groups on the pyrrole nitrogen at the non-amidine end of the molecule combined with methyl elimination in the following ring

Distamycin A analogues 5a-f (R = CnH2n+1, n = 0-5) were synthesized using our previous strategy with some improved modifications and screened for their effects on herpes simplex virus (HSV-1). Virus yield assays show that 5a-5d were potent antiviral agents whereas 5e and 5f had lower activity. Considerable cellular toxicity was however observed for 5a-5c. Thus 5d combining significant antiviral activity with moderate cellular toxicity seems to be the most promising derivative in this series.     

Simultaneous Voltammetric Determination of Captopril and Hydrochlorothiazide on a Graphene/Ferrocene Composite Carbon Paste Electrode

In this work, a voltammetric method has been developed for the simultaneous determination of captopril (CPT) and hydrochlorothiazide (HCT) in pharmaceutical combinations and clinical samples using a graphene/ferrocene composite carbon paste (GR/Fc/CP) electrode. The electrochemical behaviors of CPT and HCT were individually and simultaneously investigated at the surface of the GR/Fc/CP electrode. In differential pulse voltammetric (DPV) mode and under optimized experimental conditions, CPT and HCT gave linear responses over the concentration ranges 1.0–430 µM and 0.5–390 µM (r²>0.99), respectively. The prepared electrode could be used for simultaneous determination of CPT and HCT in some real samples.     

Antiviral agents of plant origin. II. Antiviral activity of scopadulcic acid B derivatives

Scopadulcic acid B derivatives were synthesized and their antiviral activities against herpes simplex virus type 1 (HSV-1) were examined. All the derivatives synthesized showed lower inhibitory activities against HSV-1 than scopadulcic acid B (2). Five compounds, 7, 8, 15, 16, and 18, however, had in vitro therapeutic indexes larger than 7 and were considered to merit further investigation.     

Differential pulse voltammetric determination of famotidine

A differential pulse voltammetric method for the determination of famotidine in pharmaceutical preparations is described. The method is based on electrochemical oxidation of famotidine at a glassy carbon or platinum electrode. The proposed method shows good reproducibility, and sample preparation is simple.