Determination Of Menadione Research Articles

Zsírban oldódó A-, D2-, D3-, E- és K3-vitaminok meghatározása izotóphígítással és LC-MS/MS műszeregyüttessel

The purpose of our publication is the determination of the total amount (of natural origin and added) of fat-soluble vitamins A, D2, D3 and E in low amounts in foods (wheat flour, soft drinks, effervescent tablets) and dietary supplements using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The samples were diluted with isotope-labeled derivatives of the target components (vitamin A-d6, vitamin D2-d3, vitamin D3-d3, vitamin E-d6), and after extraction and saponification, they were purified by liquid-liquid extraction. After a solvent exchange, the concentration of the vitamins was determined on a C8 HPLC column using acidic mobile phases (0.1% formic acid in water/methanol) and LC-MS/MS technique. In dietary supplements, the analysis of the fat-soluble vitamin K3 may also be important, because the use of vitamin K3 is currently not approved in human formulations. During the determination of vitamin K3, saponification is not necessary, due to its structure, alkaline hydrolysis would lead to the decomposition of vitamin K3, so this component was analyzed by a method different from the one used for the other vitamins. LC-MS/MS analysis of small amounts of vitamin K3 is more complicated than that of other vitamins due to the low sensitivity of the MS instrument to vitamin K3. The determination of vitamin K3 was therefore carried out after chemical derivatization with L-cysteine as a derivatizing reagent, also with isotope dilution and LC-MS/MS technique. After intralaboratory validation, the methods were successfully used in domestic and international proficiency tests in infant formulas and liquid vitamin preparations.

Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry Using Pseudo Multiple Reaction Monitoring.

This study aimed to develop a menadione (MD) determination method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a pseudo multiple reaction monitoring (MRM) technique, wherein two quadrupoles are used to monitor the same ion. Detection limits of 40 and 2 pg were obtained for MD and its deuterium-labeled form, respectively, whereas MD intra- and inter-assay coefficient of variation values were determined as 5.4 - 8.2%, with the corresponding recoveries equaling 90.5 - 109.6%. The developed method enables determination of MD in urine, plasma, cell extract, and culture media, demonstrating that pseudo multiple reaction monitoring can achieve quantification of compounds forming no suitable product ions, such as MD.

Validation of a Stability-Indicating Hydrophilic Interaction Liquid Chromatographic Method for the Quantitative Determination of Vitamin K3 (Menadione Sodium Bisulfite) in Injectable Solution Formulation

A simple, specific, accurate, and stability-indicating method was developed and validated for the quantitative determination of menadione sodium bisulfite in the injectable solution formulation. The method is based on zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array detector. The desired separation was achieved on the ZIC-HILIC column (250 mm × 4.6 mm, 5 μm) at 25°C temperature. The optimized mobile phase consisted of an isocratic solvent mixture of 200mM ammonium acetate (NH4AC) solution and acetonitrile (ACN) (20:80; v/v) pH-adjusted to 5.7 by glacial acetic acid. The mobile phase was fixed at 0.5 ml/min and the analytes were monitored at 261 nm using a photodiode array detector. The effects of the chromatographic conditions on the peak retention, peak USP tailing factor, and column efficiency were systematically optimized. Forced degradation experiments were carried out by exposing menadione sodium bisulfite standard and the injectable solution formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress conditions. The degradation products were well-resolved from the main peak and the excipients, thus proving that the method is a reliable, stability-indicating tool. The method was validated as per ICH and USP guidelines (USP34/NF29) and found to be adequate for the routine quantitative estimation of menadione sodium bisulfite in commercially available menadione sodium bisulfite injectable solution dosage forms.

Calixarene capped ZnS quantum dots as an optical nanoprobe for detection and determination of menadione

In this communication we report a p-sulfonatocalix[4]arene coated ZnS quantum dots "cup type" highly stable optical probe for the detection and determination of menadione (VK(3)) with high sensitivity and selectivity. The detection of VK(3) depends on supramolecular host-guest chemistry.

DETERMINATION OF MENADIONE BASED ON ITS POLAROGRAPHIC CATALYTIC WAVE IN THE PRESENCE OF POTASSIUM IODINATE

A method for the determination of menadione was proposed. In 0.2 mol/L HOAc–NaOAc (pH 4.7) buffer solution containing 4.0 × 10−3 mol/L KIO3, menadione yields a well-defined polarographic catalytic wave with a peak potential of −0.95 V (vs. SCE). The second order derivative peak current is linearly proportional to the menadione concentration in the range of 4.0 × 10−8–2.0 × 10−6mol/L with the correlation coefficient of 0.999 (n = 8). The detection limit is 2.0 × 10−8mol/L. The sensitivity of the catalytic wave is 10 times higher than that of the corresponding reduction wave in the absence of KIO3. The proposed method was used to directly determine the menadione contents in clinical injections in good agreement with the labeled amount without preseparation. The mechanism of polarographic catalytic wave of menadione was discussed. The polarographic reduction wave of menadione itself in the acetate buffer solution is ascribed to that the carbonyl group of menadione is reduced in consecutive two electrons and two protons addition to hydroquinone via semiquinone (quinone-hydroquinone) free radical intermediates. In the presence of KIO3, the carbonyl group of menadione is chemically regenerated due to oxidation of semiquinone free radical intermediates by KIO3 and a series of its derived species formed during six-electron successive reduction process. The maximum current of the first charge transfer is enhanced, and the second electroreduction step of menadione is inhibited.

Flow injection determination of vitamin K3 by a photoinduced chemiluminescent reaction

The determination of vitamin K3 using the coupling between a photochemical reaction and a chemiluminescent reaction in a flow system is described. The method is based on the photooxidation of ethanol sensitized by vitamin K3 to yield hydrogen peroxide, which is monitored through the chemiluminescent reaction with luminol catalysed by hematin. The new approach allows the determination of vitamin K3 in a wide concentration range (1 x 10(-7)-5 x 10(-4) mol l-1) with a throughput of 30 samples h-1. The applicability of the method was demonstrated by the determination of vitamin K3 in pharmaceutical preparations.

Determination of menadione in an animal feed using supercritical fluid extraction and HPLC with electrochemical detector.

Menadione (vitamin K3) is extracted from spiked rat chow using supercritical fluid carbon dioxide at 8000 psi and 60 degrees C. Quantitative extraction requires only 20 min. The extraction does not suffer from the problems associated with conventional solvent extraction of lipophilic materials from animal feeds. Menadione is determined in the extract, which does not require further cleanup, using reversed-phase high-performance liquid chromatography (HPLC) with reductive mode electrochemical detection at a silver electrode at -0.75 V vs. calomel. The minimum detectable quantity by the detector is 125 pg of menadione, and the response is linear over at least 4 orders of magnitude; however, the minimum quantity extractable is about 20 micrograms/g of feed. Repetitive extracts of a spiked feed sample over a five-day period show an average recovery of 90.5% with a relative standard deviation of 2.2% at the 1 mg/g level.

Normal-Phase Liquid Chromatographic Determination of Menadione in Animal Feeds

A simple method is presented for determination of menadione in vitamin premixes and feedstuffs by normal-phase liquid chromatography (LC). Vitamin K3 is extracted and converted to free menadione, which can be determined directly by LC analysis. Peak area or height is measured at 251 nm, and menadione is quantitated by comparison with the working standard. Menadione can be estimated with a detection limit of 2.5 ppm. Recoveries for premixes ranged from 97.3 to 98.3% and for feedstuffs from 93.7 to 96.8%. The method allows the assay of all commercial K3 compounds in pure or stabilized form and is applicable to a wide variety of feeds and premixes.

Spectrophotometric Determination of Menadione and Menadione Sodium Bisulfite

Abstract A spectrophotometric method is described for the determination of menadione and menadione sodium bisulfite in bulk and in solution for injection. The method measures the intensity of the violet color (λmax 540 nm) developed when menadione reacts with thiosemicarbazide in alkaline medium. Beer's law is obeyed in the concentration range 4-40 μg/m L (r = 0.9995). The method is simple, sensitive, and particularly suited for routine analysis of official menadione sodium bisulfite injection. Results are comparable with the USP method.

Manual and Semiautomated Spectrophotometric Determination of Vitamin K3 by Reactions with Piperidine and Malononitrile

Simple, rapid, selective, and sensitive spectrophotometric methods are described for manual and semiautomated determination of vitamin K3. These methods are based on reactions with piperidine and malononitrile whereby intense red and blue colors with maximum absorption at 510 nm (E(1%) 1 cm 150) and 580 nm (E(1%) 1 cm 155), respectively, are developed. The reactions are sensitive enough to permit the determination of 2-100 micrograms vitamin K3/mL with an average recovery of 98% and a standard deviation of 1%. There is no interference from vitamin K1 and K2, and the reduced forms of K vitamins, or from many common pharmaceutical diluents and additives.

Chromatographic-UV Spectrophotometric Determination of Menadione in Tablets

Abstract A chromatographic-UV spectrophotometric method for the determination of menadione in tablets, utilizing the conversion of menadione to menadione sodium bisulfite, has been developed. The sample is treated with sodium bisulfite and the resultant menadione sodium bisulfite is analyzed by the method of Johnson. A column prewash with CHCl3 removes impurities or degradation products present in the original menadione sample. The menadione is then eluted with an ammonia-saturated CHCl3 solution. The method worked equally well on coated and uncoated tablets and it has the advantage of determining only the amount of menadione and not degradation products present in the sample.