Simultaneous determination of ranitidine and metronidazole in pharmaceutical formulations at poly(chromotrope 2B) modified activated glassy carbon electrodes

A simple and sensitive electrochemical method for the simultaneous and quantitative detection of ranitidine (RT) and metronidazole (MT) was developed, based on a poly(chromotrope 2B) modified activated glassy carbon electrode (PCHAGCE). The PCHAGCE showed excellent electrocatalytic activity toward the reduction of both RT and MT in 0.1 mol/L phosphate buffer solution (pH 6.0). The peak-to-peak separations for the simultaneous detection of RT and MT between the two reduction waves in cyclic voltammetry were increased significantly from ∼0.1 V at activated GCE, to ∼0.55 V at PCHAGCE. By differential pulse voltammetry techniques, the reduction peak currents of RT and MT were both linear over the range of 1.0 × 10⁻⁵–4.0 × 10⁻⁴ mol/L. The detection limits (S/N = 3) were 5.4 × 10⁻⁷ mol/L and 3.3 × 10⁻⁷ mol/L for RT and MT, respectively. The modified electrode was successfully applied to the determination of RT and MT in pharmaceutical preparations and human serum as real samples with stable and reliable recovery data.     

Electrochemical behavior of paclitaxel and its determination at glassy carbon electrode

The electrochemical behavior of paclitaxel drug was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetric techniques. The oxidation process was shown to be irreversible over the pH range (3.0–10.4) and was diffusion controlled. Effects of anodic peak potential (E_p), anodic peak current (I_pa), scan rate, pH, heterogeneous rate constant (k⁰), etc have been discussed. A possible electro-oxidation mechanism was proposed. An analytical method was developed for the determination of paclitaxel in phosphate buffer solution at pH = 7.0 as a supporting electrolyte. The anodic peak current varied linearly with paclitaxel concentration in the range 1.0 × 10⁻⁶ M to 1.0 × 10⁻⁵ M with a limit of detection (LOD) of 1.23 × 10⁻⁸ M and limit of quantification (LOQ) of 4.10 × 10⁻⁸ M. The proposed method was successfully applied to the determination of paclitaxel in pure and real samples.     

Electrochemical oxidation behavior of hydrochlorothiazide on a glassy carbon electrode and its voltammetric determination in pharmaceutical formulations and biological fluids

The electrochemical oxidation behavior of hydrochlorothiazide (HCT) on a glassy carbon as a working electrode was investigated in Britton–Robinson (B–R) buffer pH 3, by using anodic stripping voltammetry (ASV) and cyclic voltammetry (CV). This drug gave a well-defined voltammetric oxidation peak at + 1200 mV versus an Ag/AgCl reference electrode. The electrochemical oxidation process was shown to be irreversible and diffusion controlled, with adsorption characterized over the entire pH range. The optimized conditions, such as accumulation time and potential, scan rate, frequency, pulse amplitude, varying of working electrodes, and instrumental parameters were studied. The calibration graph for HCT was obtained from 4 × 10⁻⁶ to 4 × 10⁻⁵ M (correlation coefficient = 0.997) using the developed electroanalytical method (ASV). The detection limit of this drug was 4.3 × 10⁻⁹ M. ASV and CV techniques with adequate precision and accuracy have been developed and applied for direct determination of HCT in commercial tablets without separation or extraction procedures and biological fluids such as urine and plasma.     

Electroanalytical study of nifedipine using activated glassy carbon electrode

The electrochemical properties of nifedipine have been investigated in aqueous solution by linear sweep and cyclic voltammetry. The method is based both on the reduction and on the oxidation of the drug at a glassy carbon electrode activated by applying a new pre-treatment. The voltammograms of nifedipine on pH, concentration and scan rate have been carefully examined. Both the electroreduction and electrooxidation of nifedipine allow its determination at pH 1.5 in the concentration range of 2×10⁻⁵–6×10⁻⁴ M and 8×10⁻⁵–1×10⁻³ M, respectively. The method has been applied to commercial samples (tablets and capsules).     

Potentiometric monitoring of cobalt in beer sample by solid contact ion selective electrode

A new solid contact cobalt selective electrode was constructed with 4-tert-butylthiacalix[4]arene as ionophore. The best performance was observed with the membrane having an ionophore/polyvinyl chloride/sodium tetraphenylborate/nitrophenyl octyl ether ratio of 3.5:33:1.5:62 (w/w; mg). The electrode, under steady-state conditions, exhibited a working concentration range of 1 × 10⁻¹ – 1 × 10⁻⁶ mol/L with a near-Nernstian slope of 25.3 mV/decade and a detection limit of 3.5 × 10⁻⁷ mol/L. The electrode had a very short response time (<10 seconds) and good reproducibility at a working pH range of 4.0–6.5. The electrode was used for 4 months without any significant change in its sensitivity. The potentiometric performance of the electrode in partially nonaqueous medium [up to 20 % (v/v) alcohol] was found satisfactory. The performance of the prepared electrode for the analysis of beer samples using direct potentiometric method is very encouraging.     

Electrochemical reduction of metronidazole at activated glassy carbon electrode and its determination in pharmaceutical dosage forms

A voltammetric method has been developed for the determination of metronidazole in dosage forms. The method is based on the electrochemical reduction of the drug at a glassy carbon electrode activated by applying a new pretreatment. The influence of pH, concentration, scan rate and presence of organic solvent and surfactant has been studied. The current is proportional to the concentration and permits the drug to be determined in the concentration range 2×10⁻⁶–6×10⁻⁴ M in Britton-Robinson buffer (pH 10). Furthermore, results obtained by the proposed method have been compared with USP XXIII procedure which involves a HPLC method.     

Determination of urea in milk based on N-bromosuccinimide–dichlorofluorescein postchemiluminescence method

A new postchemiluminescence (PCL) reaction was observed when urea was injected into the reaction mixture after the CL reaction of N-bromosuccinimide and dichlorofluorescein. A possible reaction mechanism was proposed based on the studies of the CL kinetic characteristics, CL spectra, fluorescence spectra, and other experiments. A new flow injection CL method for the determination of urea was established based on the PCL reaction. The relative standard deviation for the determination of urea was 1.3% (n = 11, c = 5.0 × 10⁻⁸ g/mL). The CL intensity responded linearly to the concentration of urea in the range 2.0 × 10⁻⁹–1.0 × 10⁻⁶ g/mL (r = 0.9992). The detection limit was 7 × 10⁻¹⁰ g/mL. The method had been applied to the determination of urea in milk with satisfactory results.     

Application of novel Ni(II) complex and ZrO2 nanoparticle as mediators for electrocatalytic determination of N-acetylcysteine in drug samples

The electrooxidation of N-acetylcysteine (N-AC) was studied by a novel Ni(II) complex modified ZrO₂ nanoparticle carbon paste electrode [Ni(II)/ZrO₂/NPs/CPE] using voltammetric methods. The results showed that Ni(II)/ZrO₂/NPs/CPE had high electrocatalytic activity for the electrooxidation of N-AC in aqueous buffer solution (pH = 7.0). The electrocatalytic oxidation peak currents increase linearly with N-AC concentrations over the concentration ranges of 0.05–600μM using square wave voltammetric methods. The detection limit for N-AC was equal to 0.009μM. The catalytic reaction rate constant, k_h, was calculated (7.01 × 10² M⁻¹ s⁻¹) using the chronoamperometry method. Finally, Ni(II)/ZrO₂/NPs/CPE was also examined as an ultrasensitive electrochemical sensor for the determination of N-AC in real samples such as tablet and urine.     

Novel discovery of schisandrin A regulating the interplay of autophagy and apoptosis in oligoasthenospermia by targeting SCF/c-kit and TRPV1 via biosensors

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10⁻¹⁵ g/L, and the quantitative limit reached 1.0 × 10⁻¹³ g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10⁻¹¹ mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10⁻¹⁰ mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.     

磺胺甲噁唑在多壁碳纳米管-Nafion修饰电极上的电催化氧化及电分析方法

运用循环伏安法(CV)、计时库仑法(CC)、计时电流法(CA)、线性扫描伏安法(LSV)及电流-时间曲线研究了磺胺甲噁唑(SMZ)在玻碳电极(GCE)及碳纳米管-Nafion修饰电极(MWCNTs-Nafion/GCE)上的电化学行为，电化学动力学性质以及电分析方法。研究结果表明，与GCE相比，SMZ在MWCNTs-Nafion/GCE上氧化峰电位负移140 mV，氧化峰电流明显增大约6倍，表明MWCNTs-Nafion/GCE对SMZ电化学氧化具有良好的催化作用。在扫描速度10～1 000 mV·s^-1时其氧化峰电流与扫描速度平方根(ν^1/2)呈良好的线性关系，表明SMZ在GCE及MWCNTs-Nafion/GCE上的伏安行为是受扩散控制的电化学过程。研究了SMZ在GCE及MWCNTs-Nafion/GCE上氧化峰电流与浓度分别在5.0×10^-5～2.5×10^-3和1.0×10^-5～6.0×10^-3 mol·L^-1呈良好线性关系，检测限分别为1.0×10^-5和5.0×10^-7 mol·L^-1。RSD在0.85%～1.98%，加样回收率在98%～101.2%。建立的SMZ含量的电化学测定方法简便快捷，测定结果令人满意。     

甲氧苄氨嘧啶(TMP)的电分析化学研究及其在药物分析中的应用

本文用微分脉冲极谱法和循环伏安法研究了甲氧苄氨嘧啶(TMP)的电化学行为,选择了最佳的测定条件,TMP的检出限可达2.0×10^-7mol/L,方法灵敏度较高,并研制了TMP-PVC膜离子选择性电极,试验了该电极的各种特性及Nernst响应范围。本法应用于制剂中TMP的测定,选择性好,干扰少,毋须分离,方法简便快速。选择电极在人尿和血清的介质中测定,也能获得良好的结果。     

多巴胺在聚对氨基吡啶修饰电极上伏安行为及其溶出伏安法测定

目的　大量抗坏血酸(AA)存在下,研究聚对氨基吡啶(POAP)化学修饰膜电极测定神经递质多巴胺(DA)。方法　用循环伏安和多阶半微分电化学方法研究对氨基吡啶在玻碳电极上的聚合和伏安行为。结果　POAP电极对DA有明显的分子识别和电催化作用。2 000倍AA存在下对DA测定无影响,检测限为4.2×10^-11 mol.L^-1(富集8 min)。结论　POAP电极使用寿命至少长达3个月,DA与AA的氧化峰分开200 mV,可用于大量AA存在下测定神经递质DA。     

Cytotoxicity and immunotoxicity of cyclopiazonic acid on human cells

In this study, in vitro cytotoxicity and immunotoxicity of the mycotoxin cyclopiazonic acid (CPA) was evaluated on human cells. To evaluate cytoxicity, several cellular targets were used (CD34+, monocytes, THP-1 and Caco-2). Monocytes were more sensitive to CPA than the THP-1 monocytic cell line after 48 h of incubation in the tested conditions. Half maximal inhibitory concentration (IC50) were determined to be 8.5 × 10⁻⁸ and 1.75 × 10⁻⁷ M for monocytes and THP1, respectively, while IC50 > 1.25 × 10⁻⁷ M was observed for Caco-2 and CD34+ cells. The CPA effect on macrophage differentiation was also examined at non-cytotoxic concentrations. The monocyte differentiation process was markedly disturbed in the presence of CPA. After 6 days of culture, CD71 expression was downregulated, while CD14 and CD11a expressions did not change. Moreover, activated macrophages showed a raised burst activity and TNF-α secretion. Overall, the results indicated that CPA exhibited toxicity on various human cellular models. Moreover, at non-cytotoxic concentrations, CPA disturbed human monocytes differentiation into macrophages. This work contributes to understanding the immunosuppressive properties of this food-related toxin.     

Activity of the enzymes of the antioxidative system in cadmium-treated Oxya chinensis (Orthoptera Acridoidae)

One purpose in this research was to determine the toxic effects of Cd on antioxidant enzymes of Oxya chinensis (Orthoptera: Acridoidae). Changes in the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and guaiacol peroxidase (GPx) were measured in O. chinensis insects injected with Cd²⁺. Fifth-nymphs of O. chinensis insects were injected with Cd²⁺ at different concentrations (0, 0.55 × 10⁻⁴, 1.10 × 10⁻⁴, 1.65 × 10⁻⁴, 2.20 × 10⁻⁴, and 2.75 × 10⁻⁴ g g⁻¹). An increase in SOD activity in O. chinensis was observed at 1.10 × 10⁻⁴ to 2.75 × 10⁻⁴ g g⁻¹ Cd²⁺. The SOD activity was lower at 2.20 × 10⁻⁴and 2.75 × 10⁻⁴ g g⁻¹ than that at 1.10 × 10⁻⁴ and 1.65 × 10⁻⁴ g g⁻¹. It appears that SOD had a positive protective effect at low Cd²⁺ concentrations, and that this effect disappeared at high Cd²⁺ concentrations. CAT activity was accelerated to varying degrees at 1.10 × 10⁻⁴ to 2.75 × 10⁻⁴ g g⁻¹ for males and at 1.10 × 10⁻⁴, 2.20 × 10⁻⁴, and 2.75 × 10⁻⁴g g⁻¹ for females. CAT showed a strong detoxification effect with all treatments. GPx activity decreased with increasing Cd²⁺ concentration with all treatments for males and at 2.20 × 10⁻⁴ and 2.65 × 10⁻⁴g g⁻¹ for females. We showed that GPx activity had a weak detoxification function with all treatments for males and at high Cd²⁺ for females. Thus, CAT had a strong detoxification effect, whereas SOD had a medium and GPx had a weak detoxification effect. Among the three enzymes, CAT played an important role in the damaging mechanisms of reactive oxygen species in O. chinensis insects. Alterations of the antioxidant enzyme level under environmental stresses are suggested as indicators of biotic and abiotic stress.     

Fluorimetric determination of chloroxine using manual and flow-injection methods

A reliable and highly sensitive method is described for the determination of chloroxine in pharmaceutical preparations. It involves the formation of a complex between chloroxine and aluminum(III) in a micellar medium. The complex is a very fluorescent species, and there is a linear relationship between chloroxine concentration and fluorescence intensity over the range {ce:inline-formula}2.0 × 10 ⁻⁸ −5.1 × 10 ⁻⁵mol1 ⁻¹{/ce:inline-formula}. The limit of detection is {ce:inline-formula}5 × 10 ⁻⁹mol1 ⁻¹{/ce:inline-formula}. The method can be easily adapted to a flow system using a three-channel manifold, the peak height being proportional to the chloroxine concentration over the range {ce:inline-formula}5.6 × 10 ⁻⁷ − 5.6 × 10 ⁻⁵mol1 ⁻¹{/ce:inline-formula}. Manual and flow-injection procedures permit the determination of chloroxine in the presence of chlorquinaldol, and have been successfully applied to the determination of chloroxine in pharmaceutical preparations.     

三丁基磷酸酯化学修饰电极伏安法测定黄嘌呤

目的：用三丁基磷酸酯化学修饰电极伏安法研究痕量黄嘌呤的测定。方法：在pH 9.5的NH₄OH—NH₄Cl缓冲溶液中,黄嘌呤在该化学修饰电极上于0.50 V(vs.SCE)左右产生一灵敏的氧化峰。结果：化学修饰膜选择性优先富集黄嘌呤,峰电流与浓度2.63×10^-7～7.89×10^-4 mol.L^-1呈线性关系,检出限为6.57×10-8 mol.L^-1 。结论：本法适用于血清、人尿中痕量黄嘌呤的测定。     

美洛昔康的吸附伏安特性

目的　研究美洛昔康(meloxicam,简称MLX)的电化学行为和电极反应机理,拟定了测定MLX的吸附伏安法。方法　用单扫示波极谱法、循环伏安法和脉冲极谱法等多种技术进行研究。结果　在HAc-NaAc(pH 4.76)底液中,MLX在汞电极上有一线性扫描还原峰,峰电位E^p=-1.19 V(vs Ag/AgCl),该峰有明显的吸附性。吸附粒子为MLX中性分子,测得MLX在汞电极上的饱和吸附量为1.53×10^-10 mol.cm^-2,每个MLX分子所占电极面积为1.08 nm²,MLX在悬汞电极上的吸附符合Frumkin等温式。测得吸附系数β=1.65×10⁶,电子转移数(n)为2,不可逆吸附的电子转移系数(α)为0.84,表面电极反应的速率常数k_s=0.19.s^-1。建立了吸附伏安法测定MLX的最佳条件,检出限为1.0×10^-9 mol.L^-1。结论　证实该体系为具有吸附性的不可逆过程。     

CYP-450 isoenzymes catalyze the generation of hazardous aromatic amines after reaction with the azo dye Sudan III

This work describes the mutagenic response of Sudan III, an adulterant food dye, using Salmonella typhimurium assay and the generation of hazardous aromatic amines after different oxidation methods of this azo dye. For that, we used metabolic activation by S9, catalytic oxidation by ironporphyrin and electrochemistry oxidation in order to simulate endogenous oxidation conditions. The oxidation reactions promoted discoloration from 65% to 95% of Sudan III at 1 × 10⁻⁴ mol L⁻¹ and generation of 7.6 × 10⁻⁷ mol L⁻¹ to 0.31 × 10⁻⁴ mol L⁻¹ of aniline, o-anisidine, 2-methoxi-5-methylaniline, 4-aminobiphenyl, 4,4′-oxydianiline; 4,4′-diaminodiphenylmethane and 2,6-dimethylaniline. The results were confirmed by LC–MS–MS experiments. We also correlate the mutagenic effects of Sudan III using S. typhimurium with the strain TA1535 in the presence of exogenous metabolic activation (S9) with the metabolization products of this compound. Our findings clearly indicate that aromatic amines are formed due to oxidative reactions that can be promoted by hepatic cells, after the ingestion of Sudan III. Considering that, the use of azo compounds as food dyestuffs should be carefully controlled.     

Interaction of 3′ -O-caffeoyl d-quinic acid with human serum albumin

The interaction of chlorogenic acid (CGA) with human serum albumin (HSA) was studied from the viewpoint of thermodynamics and mechanism of binding at pH 6.0. The association constants (K_a) for the HSA-CGA interaction at 10, 25 and 40° C were 6.0 × 10⁴, 9.0 × 10³ and 2 × 10⁴ M^?1, resulting in AG of -6.21, -5.80, -6.32 kcal/mol, respectively. These high K_a -values showed that the interaction between CGA and HSA is strong, endothermic and entropically driven. Binding of chlorogenic acid induces conformational change in HSA as indicated by quenching of fluorescence emission intensity along with a red shift in the emission maxima from 338 to 350 mm. This suggested the involvement of the lone tryptophan residue in the region of binding. Far-ultraviolet circular dichroic data showed a decrease in the α-helical content of HSA from 56 to 50% upon binding of CGA. These data are also supported by the decrease in the apparent Tm of HSA by 4°C upon binding of CGA causing destabilization of the HSA molecule. The kinetics of the interaction involves a single step in the binding, and the kinetic curve attains equilibrium within 180 ± 5 s. Data on caffeic acid (CA) and quinic acid (QA), which are the hydrolysis products of the bidentate CGA molecule, indicate that CA interacts more strongly than CGA. CA binds with an association constant of 8 × 10⁴ M^?1and with a maximum number of binding sites of four. Microcalorimetric investigation of the interaction of these ligands with HSA suggests that the strength of binding follows the order CA?CGA?>QA with a single class of binding sites. The effect of temperature on the binding of CGA to HSA showed that the interaction is dominated by hydrophobic forces and hydrogen bonding.     

Voltammetric determination of sulfamethoxazole at a multiwalled carbon nanotube modified glassy carbon sensor and its application studies

Sulfamethoxazole (SMX) is an anti‐bacterial sulfonamide. It prevents the formation of dihydrofolic acid, a compound that bacteria need in order to survive. The present work details the voltammetric analysis of SMX at a multiwalled carbon nanotube (MWCNT)‐Nafion modified glassy carbon electrode (GCE). Sulfamethoxazole gives a well defined oxidation peak at 0.74 V in 0.1 M phosphate buffer solution (PBS) of pH 8.0. The experimental parameters such as the amount of MWCNT‐Nafion suspension, the pH of the supporting electrolyte and scan rate were optimized and a direct electrochemical method for the determination of SMX was developed. Under optimum conditions the oxidation peak current is linear to the concentration of SMX in the range 1 × 10^?2 ? 5 × 10^?5 M with a detection limit of 1 × 10^?5 M. The MWCNT/GCE showed good stability, selectivity and was successfully used to quantify SMX in pharmaceutical formulations and urine sample. Copyright © 2009 John Wiley & Sons, Ltd.