Development and validation of a high‐performance liquid chromatography method for the simultaneous determination of aspirin and folic acid from nano‐particulate systems

Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive analytical method exists to simultaneously quantify the two drugs when released from polymer‐based nanoparticles. Thus, a rapid, highly sensitive method of high‐performance liquid chromatography analysis to simultaneously detect low quantities of aspirin (hydrolyzed to salicylic acid, the active moiety) and folic acid released from biodegradable polylactide‐co‐glycolide (PLGA) copolymer nanoparticles was developed. Analysis was done on a reversed‐phase C₁₈ column using a photodiode array detector at wavelengths of 233 nm (salicylic acid) and 277 nm (folic acid). The mobile phase consisted of acetonitrile–0.1% trifluoroacetic acid mixture programmed for a 30 min gradient elution analysis. In the range of 0.1–100 μg/mL, the assay showed good linearity for salicylic acid (R² = 0.9996) and folic acid (R² = 0.9998). The method demonstrated good reproducibility, intra‐ and inter‐day precision and accuracy (99.67, 100.1%) and low values of detection (0.03, 0.01 μg/mL) and quantitation (0.1 and 0.05 μg/mL) for salicylic acid and folic acid, respectively. The suitability of the method was demonstrated by simultaneously determining salicylic acid and folic acid released from PLGA nanoparticles. Copyright © 2009 John Wiley & Sons, Ltd.     

An investigation of the chemiluminescence reaction in the sodium hypochlorite–folic acid–emicarbazide hydrochloride system

A chemiluminescence method for the determination of folic acid by the sodium hypochlorite–folic acid–semicarbazide hydrochloride system with a new flow injection technique has been established. The new method can perform simple, sensitive and rapid determinations of folic acid. The response to the concentration of folic acid, in the range of 1.0×10⁻⁷5.0×10⁻⁵ g/ml, is linear. The relative standard deviation of the method is 2.3% (C_s=4.0×10⁻⁶ g/ml, n=11). The detection limit is 2.7×10⁻⁸ g/ml. This method is suitable for automatic and continuous analysis, and has been successfully tested for the determination of folic acid in a folic acid tablet.     

Fluorescent carbon dots derived from lactose for assaying folic acid

The fluorescent carbon dots were successfully synthesized by simply heating the mixture of lactose and Na OH solution. The as-synthesized carbon dots had been systematically characterized by fluorescence, Fourier transform infrared(FTIR), high resolution transmission electron microscopy(HR-TEM) and ~(13)C NMR. Since the fluorescence of the carbon dots was efficiently quenched by folic acid, the carbon dots were employed as selective fluorescence probes for detecting folic acid, depending on the formation of hydrogen bond among the functional group of folic acid(–OH, –COOH and –NH_2) and –OH and –COOH of the carbon dots. Moreover, the decrease of fluorescence intensity was capable of detecting folic acid in a linear range of 6×10~(-5)–8×10~(-8) mol/L with a detection limit of 1.2×10~(-9)mol/L at a signal-to-noise ratio of 3, suggesting a promising assay for folic acid. Significantly, the practicability of this fluorescence probe to assay folic acid in human urine samples was further evaluated.     

Amperometric Folic Acid Quantification Using a Supramolecular Tetraruthenated Nickel Porphyrin µ‐Peroxo‐Bridged Matrix Modified Electrode Associated to Batch Injection Analysis

A supramolecular Nickel (II) porphyrin complex containing four pyridyl‐bis(2,2′‐bipyridyl)chloro ruthenium meso substituents was submitted to successive voltammetric cycles in high alkaline media to produce a supramolecular matrix with Nickel centers linked by µ‐peroxo bridges, producing a highly stable thin film able to act as redox mediator for electrocatalytic oxidation of folic acid. The characterization of electrode surface material was performed by Scanning Electron Microscopy and Electrochemical Impedance Spectroscopy. The modified electrode was inserted into a batch injection electrochemical cell used for the rapid and precise quantification of folic acid in pharmaceutical products. The favorable hydrodynamic conditions provided by amperometry‐BIA association allowed a very high throughput with good linear range (1 to 200 µmol L^?1) and low detection limit (7.37×10^?7 mol L^?1). The electrochemical method was applied to the quantification of folic acid in different tablet samples. The results were comparable with values indicated by the manufacturer and those found using high HPLC according to the Brazilian Pharmacopoeia; commercial samples were submitted to a procedure in order to remove lactose of tablets, since carbohydrates act as interfering species. This procedure together with the electrochemical method showed to be simple, rapid, efficient and an appropriate alternative for quantifying this compound in real samples.     

Determination of Folic Acid at a Bismuth Film Electrode by Adsorptive Stripping Voltammetry

This article reports a new simple and sensitive method for the determination of folic acid by adsorptive stripping voltammetry. The method is based on the accumulation of folic acid at a bismuth film plated in situ on a glassy carbon substrate. In order to stabilize bismuth ions, sodium potassium tartrate was added to the supporting electrolyte. The bismuth film formation and folic acid accumulation conditions were optimized and measurements were carried without solution deaeration. The calibration graph was linear from 5 × 10^?10 to 2 × 10^?8 mole per liter with an accumulation time of 180 seconds with a limit of detection of 2 × 10^?10 mole per liter. The relative standard deviation for 5 × 10^?9 mole per liter of folic acid was 3.1 percent (n = 5). The method was successfully applied for determination of folic acid in pharmaceutical preparations.     

Novel Copper(II)-Selective Potentiometric Sensor Based on a Folic Acid-Functionalized Carbon Nanotube Material

Abstract

A folic acid-functionalized carbon nanotube nanomaterial was prepared by immobilizing folic acid molecules on the carbon nanotubes through covalent bonds. The material was characterized using Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy and scanning electron microscopy. Fourier transform infrared spectroscopy confirmed that folic acid molecules were grafted on the carbon nanotube surfaces through the amide bonds between the carboxylic acid functional groups of the oxidized carbon nanotubes and the amine groups of the folic acid molecules. The folic acid molecules bonded to carbon nanotube surfaces led to appreciable changes in the morphology. By using currently obtained folic acid-functionalized carbon nanotube nanomaterial as electroactive material in a polyvinyl chloride membrane, a potentiometric copper (II)-selective sensor was developed. Membrane optimization studies showed that the composition exhibiting the best potentiometric properties was 4.0% (w/w) folic acid–carbon nanotube, 64.0% (w/w) o-nitrophenyl octylether, and 32.0% (w/w) polyvinyl chloride. The developed sensor displayed a linear response in the copper (II) concentration ranging from 1.0?×?10^–6 to 1.0?×?10^–1 M with a correlation coefficient of 0.9993 and a slope of 29.8?±?0.6?mV/decade of activity. The response time, detection limit, and pH working range were determined to be 4?s, 3.8?×?10^–7 M and 4.0–8.0, respectively. The developed sensor showed highly selective and satisfactory potentiometric response for the determination of copper (II) in a Turkish coin.     

Determination of Folic Acid by Adsorptive Stripping Voltammetry at a Lead Film Electrode

An adsorptive stripping voltammetric procedure for the determination of folic acid at an in situ plated lead film electrode was described. Formation of lead film on a glassy carbon substrate and accumulation of folic acid was performed simultaneously from an acetate buffer solution of pH 5.6 at the potential ?0.88 V. The measurements were carried out from aerated solutions. The calibration graph for an accumulation time of 300 s was linear from 2×10^?9 to 5×10^?8 mol L^?1. The detection limit was 7×10^?10 mol L^?1, the relative standard deviation for 2×10^?8 mol L^?1 of folic acid was 3.9%. The proposed procedure was applied to folic acid determinations in pharmaceutical preparations.     

Synthesis and characterization of a colloidal novel folic acid?C??-cyclodextrin conjugate for targeted drug delivery

A novel folic acid?C??-cyclodextrin (??-CD) conjugate was synthesized and preliminarily characterized by ¹H NMR, ESI-MS, and MALDI-MS. ¹H NMR shows the presence of ??- and ??-conjugates which are generated by ??-CD linkage in turn with both carboxylic functions of folic acid. Moreover ROESY evidences supramolecular interactions between the benzene ring of the folic acid and the ??-CD cavity. DOSY suggests that ethylenediamine derived ??-CD?Cfolic acid forms a colloidal dispersion difficult to purify from free folic acid. An analysis of self-diffusion coefficient (D_s) of the three species (??-, ??-conjugates, and free folic acid) and relaxation times (T₁ and T₂) is reported to tentatively explain the colloidal behaviour of the new species in an aqueous solution.     

Determination of folic acid by adsorptive stripping voltammetry at the static mercury drop electrode

Folic acid can be determined at nanomolar concentrations by controlled adsorptive accumulation of folic acid on a static mercury drop electrode held at ?0.3 V vs. Ag/AgCl followed by reduction of the surface species. In 0.1 M sulfuric acid, a cathodic scan gives peaks at ?0.47 v and ?0.75 V vs. Ag/Agcl; the latter peak provides greater sensitivity. Differential-pulse stripping is shown to be superior to normal-pulse and d.c. stripping. After a 5-min preconcentration, the detection limit is about 1 × 10^?10 M folic acid. The adsorptive stripping response is evaluated with respect to concentration dependence, preconcentration time and potential, solution acidity and the presence of gelatin and bromide. The relative standard deviation at the 5 × 10^?8 M level is 1.2%. This method is applied to the determination of folic acid in pharmaceutical tablets.     

Über Pterinchemie. 49. Mitteilung. Eine neue Synthese von 5-Formyl-6, 7-dimethyl-5,6,7,8-tetrahydropterin und 5,6,7-Trimethyl-5,6,7,8-tetrahydropterin

Starting with 5-formyl-6,7-dimethyl-5,6,7,8-tetrahydropterine (II), a new synthesis of 5,6,7-trimethyl-5,6,7,8-tetrahydropterine (III) is described. Thereby the chemical behaviour of the 5-formyl group in II is investigated, in order to enable the unequivocal differentiation between formylation at position 5 and at position 10 in folic and tetrahydrofolic acid derivatives. ¹³C-NMR. spectra of II and III are discussed.     

Application of a Single-Wall Carbon Nano-Tube Film Electrode to the Determination of Trace Amounts of Folic Acid

Single-wall carbon nano-tubes were used to modify the surface of a glassy carbon electrode (GC) and applied in the determination of folic acid with voltammetry. The experiments demonstrated that the presence of a carbon nano-tube film on the electrode greatly increased the reduction peak current of folic acid. Cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were used in a comparative investigation of the electrochemical reduction of folic acid with the film electrode. Effects of pH on the peak current and the peak potential were studied in the pH range of 4.0–8.0 with Britton-Robinson buffer solution. The reduction peak current was found to be linearly related to folic acid concentration over the range of 1 × 10⁻⁸ to 1 × 10⁻⁴ mol L⁻¹ with a detection limit of 1 × 10⁻⁹ mol L⁻¹ after 5 min accumulation. The film electrode provides an efficient way for eliminating interferences from some inorganic and organic species in the solution. The high sensitivity, selectivity and stability of the film electrode demonstrate its practical application from a simple and rapid determination of folic acid in tablets.     

Highly Sensitive Spectrofluorimetric Determination of Trace Amounts of Folic Acid using a Oxytetracycline-Terbium(III) Probe

Abstract

A new spectrofluorimetric method was developed for the determination of trace amounts of folic acid using oxytetracycline–terbium ion complex as a fluorescent probe. In the buffer solution of pH 6.00, folic acid remarkably reduced the fluorescence intensity of the oxytetracycline–terbium complex at λ = 545 nm. The reduced fluorescence intensity of the Tb³⁺ ion was proportional to the concentration of folic acid. Optimum conditions for the determination of folic acid were investigated. This method was simple, practical, and relatively free of interference from coexisting substances. Furthermore, it was successfully applied to assess folic acid in tablet, injection, and urine samples.     

A general method for synthesis of folic acid, its conjugates and analogues (author's transl)]

A general method for synthesis of folic acid, its conjugates and analogues . A new and general method for the synthesis of folic acid, folic acid conjugates and folic acid analogues is described. The key step, i.e. the condensation of N(2′)-acetyl-6-formyl-pterine (I: R¹ ? COCH₃) with aminoaryl derivatives II, is achieved by refluxing in absolute ethanol to afford the azomethines III. NaBH₄-reduction followed by basic hydrolysis gives pure V products in high yield, free from 7-isomers.     

Radioenzymatic determination of subpicomole quantities of folic acid and dihydrofolate based on differential reduction by dihydrofolate reductase

A sensitive method for the determination of folic acid in the presence of dihydrofolate has been described. The analysis is based on the difference in reactivity of dihydrofolate reductase toward folic acid and dihydrofolate. The tetrahydrofolate formed was measured by stoichiometric entrapment into a covalent, ternary complex with thymidylate synthase and [³H]fluorodeoxyuridylate. Differentiation between folic acid and dihydrofolate was accomplished by the use of two levels of dihydrofolate reductase. Recovery of both folic acid and dihydrofolate was quantitative in the range of 0.1 to 2.0 pmol.     

Direct observation for photophysical and photochemical processes of folic acid in DMSO solution

Using the fast optical technique of laser flash photolysis by a kinetic absorption detector, the photophysical and photochemical processes of folic acid have been observed. By comparison of transient absorptions from photolysis between folic acid and its components, pteroic acid, pterin and 6-carboxypterin, it has been demonstrated that electron-transfer reactions from 4-aminobenzoyl group to the triplet pterin moiety occur through intra- and inter-molecular processes of folic acid. The intermolecular electron-transfer reaction is suggested to be mediated by two tautomers of triplet states of folic acid, lactim and lactam, in different rate constants, 1.4 × 10⁹ and 1.6 × 10⁸ M⁻¹ s⁻¹, respectively.     

基于纳米结构的电化学传感器用于伏安法测定苄丝肼、尿酸和叶酸(英文)

A carbon paste electrode modified with carbon nanotubes and ferrocene was fabricated.An electrochemical study of the modified electrode and an investigation into its efficiency for the electrocatalytic oxidation of benserazide,uric acid and folic acid were undertaken.The electrode was also used to study the electrocatalytic oxidation of benserazide using cyclic voltammetry,chronoamperometry,and square wave voltammetry(SWV).We found that the oxidation of benserazide at the surface of the modified electrode occurs at a potential about 285 mV lower than that of unmodified carbon paste electrode.SWV gave a linear dynamic range from 8.0×10-7 to 7.0×10 4 mol/L.The detection limit was 1.0×10-7 mol/L for benserazide.This modified electrode was used for the determination of benserazide,uric acid,and folic acid in an urine sample.     

Sensitive Simultaneous Determination of Rutin and Folic Acid with the Use of a Solid Lead Electrode by Means of Adsorptive Stripping Voltammetry

In this article a solid lead electrode (PbE) was utilized for the first time for determination of organic substances by means of adsorptive stripping voltammetry. A new procedure of simultaneous determination of rutin and folic acid was developed. Two well shaped and well separated reduction signals of rutin and folic acid were obtained with the use of PbE. The optimization of analytical procedure was presented. The calibration graphs for rutin and folic acid for an accumulation time of 120 s were linear in the ranges from 2×10^?9 to 1×10^?7 mol L^?1 and from 2×10^?9 to 5×10^?8 mol L^?1, respectively. The obtained detection limits for rutin and folic acid determination following accumulation time of 120 s were 7.9×10^?10 and 8.4×10^?10 mol L^?1. Potential interference effects were investigated. The proposed procedure was used for analysis of pharmaceutical preparations with satisfactory results showing practical applications. The analytical parameters of the proposed procedure were compared with other voltammetric procedures of mentioned substances determination.     

Electrocatalytic Oxidation of Folic Acid on Carbon Paste Electrode Modified by Nickel Ions Dispersed into Poly(o‐anisidine) Film

Poly(o‐anisidine) (POA) was formed by successive cyclic voltammetry in monomer solution containing sodium dodecyl sulfate (SDS) at the surface of carbon paste electrode. Then Ni(II) ions were incorporated to electrode by immersion of the polymeric modified electrode having amine group in 0.1 M Ni(II) ion solution. Cyclic voltammetric and chronoamperometric experiments were used for the electrochemical study of this modified electrode; a good redox behavior of Ni(OH)₂/NiOOH couple at the surface of electrode can be observed. The capability of this modified electrode for catalytic oxidation of folic acid was demonstrated. The amount of α and surface coverage (Γ*) of the redox species and catalytic chemical reaction rate constant (k) for folic acid oxidation were calculated. The catalytic oxidation peak current of folic acid was linearly dependent on its concentration and a linear calibration curve was obtained in the range of 0.1 to 5 mM with a correlation coefficient of 0.9994. The limit of detection (3σ) was determined as 0.091 mM. This electrocatalytic oxidation was used as simple, selective and precise voltammetric method for determination of folic acid in pharmaceutical preparations.     

Fluorometry of singlet oxygen generated via a photosensitized reaction using folic acid and methotrexate

A method for the fluorometry of singlet oxygen (¹O₂) using less fluorescent folic acid and its analogue, methotrexate (MTX), was examined. Folic acid and MTX were decomposed into a strongly fluorescent pteridine compound via a photosensitized reaction by ¹O₂-generating photosensitizers in a deuterium oxide solution. The fluorescence intensity increased in proportion to the irradiation time or the number of photons absorbed by the photosensitizer. This method using the fluorescence enhancement of these folic acid analogues can be applied to determine the quantum yield of ¹O₂ generated through a photosensitized reaction in deuterium oxide. The background fluorescence of MTX is quite smaller than that of folic acid, indicating that MTX can be used for the more sensitive detection of ¹O₂. Figure (DOC 37.0 KB)     

Development of a highly sensitive and selective hyphenated technique (molecularly imprinted micro-solid phase extraction fiber-molecularly imprinted polymer fiber sensor) for ultratrace analysis of folic acid

A simple polymerization strategy is reported in this work which allows molecularly imprinted polymeric fiber (monolith) fabrication for direct use in sensing devices. This is advantageous for achieving higher degree of enrichment of target analyte (folic acid) from the complex matrices of real samples, without any surface fouling, cross-reactivity, and non-specific (false-positive) contributions. In order to measure serum folic acid at ultratrace level to detect spina bifida, a neural tube defect in mother, and other acute cases of proteomic diseases, the hyphenation between molecularly imprinted micro-solid phase extraction fiber and a complementary molecularly imprinted polymer-carbon composite fiber sensor has been found quite efficient. The primitive diagnosis of many chronic diseases is feasible by estimating folic acid as biomarker, with the detection limit as low as 0.0036 ng mL⁻¹ (relative standard deviation = 0.13%, signal/noise = 3) in human blood serum.