Folic Acid In Pharmaceutical Preparations Research Articles

Batch and Flow injection Spectrophotometric Methods For Determination of Folic acid in Pharmaceutical Preparations using Cerium(IV) ammonium sulphate(CAS) as an oxidant.

A simple, rapid and sensitive batch and flow injection spectrophotometric methods have been developed for the determination of folic acid (FA) in pure form and in its pharmaceutical preparations. The proposed methods involve the addition of a measured excess of cerium (IV) ammonium sulphate (CAS) in acidic medium followed by determination of unreacted CAS by reacting with a fixed amount of methylene blue (MB) and measuring the absorbance at 665 nm. The optimum reaction conditions and other analytical parameters have been evaluated. Linearity was observed from 1-10 and 4.0-20.0 μg/ml folic acid by batch and flow injection procedures, respectively. Statistical analysis of the results and comparison with results by the British Pharmacopoeia method are also reported.

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.

Determination of folates by HPLC‐chemiluminescence using a ruthenium(II)–cerium(IV) system, and its application to pharmaceutical preparations and supplements

A chemiluminescence (CL) reaction of folic acid (FA) with ruthenium (II) and cerium (IV) was applied to quantify FA-related compounds such as FA, dihydrofolic acid, tetrahydrofolic acid, 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid and methotrexate (MTX). Among the FAs, 5-methyltetrahydrofolic acid provided the highest CL intensity. HPLC-CL detection of FA was applied to quantify FA in pharmaceutical preparations and supplements. Analytical samples were separated on a semi-micro ODS column with a mixture of 20 mM phosphate buffer (pH 5.7) and acetonitrile (94 : 6, v/v %). The separated samples were mixed with a post-column CL reagent consisting of 1.5 mM Ru(bipy)3 (2+) and 1.0 mM Ce(SO4)2 , then the generated CL was monitored. The calibration range for FA was 10-100 μM and the limit of detection was 1.34 μM (signal-to-noise ratio of 3). Repeatabilities were 4.2, 4.6 and 5.0 RSD% (10, 25, 50 μM), and the recoveries for FA supplement, vitamin B complex supplement and FA-containing medication (tablet) were 102.4 ± 10.5, 103.3 ± 13.3 and 100.3 ± 8.5%, respectively. The described method is robust against changes in the chromatographic parameters of ± 3.3 or ± 1.5%. The measured FA content corresponded well to the labeled content of FA-containing products (100.6-104.9%), demonstrating the precision and accuracy of this method for the evaluation of FA pharmaceutical preparations.

Chemiluminescence determination of folic acid by a flow injection analysis assembly

A flow injection (FI) method is reported for the determination of folic acid by chemiluminescence method. This method is based on the reaction of folic acid with Ru(bipy)32+ and Ce(IV) to produce chemiluminescence. The calibration curve was linear over the range of 2.5×10−5–3.1×10−7mol/L with a detection limit of 2.3×10−8mol/L (S/N=3). The relative standard deviation of 1.0×10−6mol/L folic acid was found 3.5% (n=11). The influences of potential interfering substances were studied. The recovery was higher than 95.3%. The method was accurate, sensitive, and effective for assay of folic acid. This CL method was successfully applied to the determination of folic acid in pharmaceutical preparations. The mechanism of CL reaction was also studied.

A validated ultra high pressure liquid chromatographic method for qualification and quantification of folic acid in pharmaceutical preparations

A fully validated UHPLC method for the identification and quantification of folic acid in pharmaceutical preparations was developed. The starting conditions for the development were calculated starting from the HPLC conditions of a validated method. These start conditions were tested on four different UHPLC columns: Grace Vision HT™ C18-P, C18, C18-HL and C18-B (2 mm × 100 mm, 1.5 μm). After selection of the stationary phase, the method was further optimised by testing two aqueous and two organic phases and by adapting to a gradient method. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. A UHPLC method was obtained for the identification and quantification of folic acid in pharmaceutical preparations, which will cut analysis times and solvent consumption.

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

AbstractPoly(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.

Determination of folic acid by chemiluminescence based on peroxomonosulfate-cobalt(II) system

Based on the chemiluminescence (CL) phenomena of folic acid in peroxomonosulfate-cobalt(II) system, a rapid and sensitive CL method was developed for determination of folic acid in pharmaceutical preparations and its urinary metabolism processes. Under the optimum conditions, the relative CL intensity was linear over the concentration ranging from 10 −9 to 8 × 10 −7 mol L −1 ( R 2 = 0.9991) with a detection limit as low as 6 × 10 −10 mol L −1 (S/N = 3) and relative standard deviation was 2.63% for 2 × 10 −8 mol L −1 folic acid ( n = 11). This method has been successfully applied to the determination of folic acid in tablets and human urine. The blank CL emission was yielded owing to the formation of singlet oxygen molecular pair from the quenching experiment of 1,4-diazabicyclo[2.2.2]octane, and pterine-6-carboxylic acid might be the degradation intermediate in this system and it also acts an energy acceptor and sensitizes the chemiluminescence based on the studies of the CL and fluorescence spectra.

Solid-phase reactor flow-injection on-line oxidizing spectrofluorimetry for determination and dissolution studies of folic acid

A simple, sensitive and specific flow-injection spectrofluorimetric method has been developed for the determination of folic acid in pharmaceuticals. The method is based on use of a lead dioxide solid-phase reactor for on-line oxidation of folic acid into a strongly fluorescent compound with a maximum excitation wavelength of 281 nm and an emission wavelength of 450 nm. Under optimum conditions the fluorescence intensity of oxidation product is proportional to the concentration of folic acid over the range 0.008-2.5 microg mL(-1). The detection limit is 0.0001 microg mL(-1), the relative standard deviation is 0.85% for 11 replicate determinations of 0.05 microg mL(-1) folic acid, and the sample throughput is 20 h(-1). In combination with an on-line filter and dilution, an automated drug-dissolution system was established. The proposed method has been successfully applied to the determination of folic acid in pharmaceutical preparations and dissolution testing.

Chemiluminescence inhibition assay for folic acid using flow injection analysis.

A new flow injection method for the determination of folic acid is described. A fast oxidation reaction occurred when folic acid was mixed with potassium ferricyanide generating ferrocyanide which then inhibited the chemiluminescent reaction of ferricyanide and luminol in alkaline medium. The decrease of chemiluminescence intensity was correlated with the folic acid concentration in the range 0.1-21 microg/mL; the detection limit for the assay was 0.03 microg/mL (3sigma). A complete analysis of folic acid, including sampling and washing, could be performed within 2 min with a relative standard deviation of less than 4.0%. The proposed method has been applied successfully to the determination of folic acid in pharmaceutical preparations.

Spectrophotometric determination of folic acid in pharmaceutical preparations by coupling reactions with iminodibenzyl or 3-aminophenol or sodium molybdate–pyrocatechol

Novel coupling reagents are used for the simple and sensitive spectrophotometric determination of folic acid either in pure form or in its pharmaceutical preparations. The methods are based on the probable diazotization of the p-aminobenzoylglutamic acid obtained after reductive clevage of folic acid, followed by either coupling with iminodibenzyl to give a violet product with λ max of 580 nm or coupling with 3-aminophenol to produce an orange yellow-colored product with λ max of 460 nm. Sodium molybdate and pyrocatechol are used in the third method and the pale red-colored product formed has a λ max of 490 nm. The methods are highly reproducible and have been applied to the determination of folic acid in tablets and the results compare favorably with the official method. Common excipients used as additives in pharmaceutical preparations do not interfere in the proposed methods.

Chemiluminescence flow sensor for folic acid with immobilized reagents

A novel chemiluminescence (CL) sensor for folic acid combined flow-injection (FI) technology was presented in this paper. The analytical reagents involved in the CL reaction, including luminol and hexacyanoferrate(III), were both immobilized on an anion-exchange column in FI system. The CL signal produced by the reaction between luminol and hexacyanoferrate(III), which were eluted from the column through sodium phosphate injection, was decreased in the presence of folic acid. The CL emission was correlated with the folic acid concentration in the range from 0.01 to 15 μg ml −1, and the detection limit was 3.5 ng ml −1 folic acid (3 σ). At a flow rate of 2.0 ml min −1, including sampling and washing, could be performed in 2 min with a relative standard deviation of <2.5%. The flow sensor could be reused more than 300 times and has been applied to the analysis of folic acid in pharmaceutical preparations, and the recovery was from 97.4% to 100.4%.

Simultaneous square-wave voltammetric determination of riboflavin and folic acid in pharmaceutical preparations

The square-wave voltammetric (SWV) behaviour of riboflavin and folic acid was studied at a static mercury drop electrode by square wave voltammetry. In 0.05M KCl (pH 5.89) a cathodic scan gave peaks at — 0.56 and — 0.87 V vs. Ag/AgCl for riboflavin and folic acid, respectively. The reduction peak currents are linearly dependent on the concentration of vitamins. Both vitamins can be simultaneously determined from the same voltammogram. The method proposed for the determination of riboflavin and folic acid in multivitamin tablets is very simple, rapid and does not involve time-consuming separation steps. The average contents of riboflavin and folic acid were found to be 14.8 ± 1.26% and 1.46 ± 2.66%, for tablet A and 9.86 ±1.40% and 1.47 ± 2.0% for tablet B, respectively.

Micellar-enhanced synchronous-derivative fluorescence determination of derivatized folic acid in pharmaceutical preparations

A sensitive and inexpensive micellar-enhanced synchronous-derivative spectrofluorimetric method is described for the determination of folic acid in pharmaceutical preparations. The method is based upon derivatization of the vitamin with fluorescamine in acid solution and enhancement of the fluorescence with a surfactant. Linear fluorimetric analytical curves were obtained for folic acid concentrations of 0.05–6 μg ml −1 (detection limit 0.012 μg ml −1); the RSD for 1 μg ml −1 of folic acid was 2.82%. The method has been applied to the determination of folic acid synthetic mixtures and pharmaceutical preparations.

Adsorptive stripping voltammetric determination of folic acid in pharmaceutical preparations

AbstractAn adsorptive stripping voltammetric (AdSV) procedure is proposed for determination of folic acid (FA) in cores and coated pellets of Hemofer (FA/iron tablet). The adsorptive stripping response was evaluated with respect to the electrolyte solution, the accumulation time and potential, and the concentration dependence. The relationship between ip and FA concentration was linear over the range 1 × 10−8 to 5 × 10−7 M FA. The conditions of cores and pellets preparation for analysis were established. The relative standard deviation is 2.4% for a content of FA of 0.35 mg per core (n = 5).

Polarographic determination of folic acid in pharmaceutical preparations

A.c. polarograms of folie acid recorded from acetate buffer pH 5.5 exhibit a very welldefined wave at the dropping mercury electrode. The current is diffusion-controlled and proportional to the concentration; the optimal range of measurement is 0-24̄ μg ml -1. Two electrons and two hydrogen ions are involved in the reduction. With the phase-sensitive a.c. polarographic method, the calibration graph is linear in the 2 × 10 -8—2 × 10 -6 M range. The method proposed for the determination of folic acid in tablets is very simple and rapid, and does not involve time-consuming separation of iron salts and insoluble constituents in the tablets.

Colorimetric determination of folic acid in pharmaceutical preparations.

A colorimetric method, based on colour development with 1,2-naphtho-quinone-4-sulphonic acid, sodium salt, has been developed for the determination of folic acid. The method depends on the availability of the primary amino group that is liberated on reduction of folic acid. The colour produced has an absorbance maximum at 485 nm and obeys Beer's law in the concentration range 11·7 to 58·7 µg ml–1. The method has been used successfully for assaying folic acid, tablets containing folic acid alone or in combination with iron and vitamin B12, and injections of folic acid.

The Chemical Determination of Folic Acid in Pharmaceutical Preparations

The procedure of Hutchings, et al., has been modified for use with pharmaceutical preparations containing colored materials such as iron salts, liver, vitamins, etc. Concentrations of folic acid as low as 0.01 per cent can be accurately determined in the presence of these colored materials by using the modified procedure. Illustrations are given of how the method was evolved. A curve was prepared for commercial folic acid and water solution using para-amino benzoyl glutamic acid as a primary standard. One by one the colored ingredients were added and the curves examined in turn. The effect of increments of folic acid was studied. Assays were checked at different dilutions. Finally, aged samples of dark solutions were tested by both the chemical and microbiological assays and the results compared.