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The Analysis of Menadione in Feed Premixes Using Supercritical Fluid

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The Analysis of Menadione in Feed Premixes Using Supercritical Fluid The Analysis of Menadione in Feed Premixes Using Supercritical Fluid Chromatography Daniel Hengst, Hannah Poe and Chad Scheurell Eurofins Food Integrity & Innovation, Madison, WI Abstract Methods Analysis Menadione is a synthetic form of Vitamin K used to supplement animal Menadione is routinely analyzed using well-established techniques. A During the extraction, Menadione Sodium Bisulfite is converted to feeds. The K vitamins, which include Menadione (Vitamin K3), common procedure for sample extraction includes agitating the sample Menadione. The analyte is resolved using Supercritical Fluid Phylloquinone (Vitamin K1), and Menaquinone (Vitamin K2), have in an acidic aqueous solvent mixture, converting Menadione Sodium Chromatography (Shimadzu Nexera UC) on a Cosmosil π Napthelene numerous physiological roles, with the primary role being a cofactor in Bisulfite to Menadione through pH manipulation followed by partition column (4.6 x 250 mm, 5µ) with a linear gradient of methanol and the coagulation of blood. Accurate analysis of Menadione in feed into a nonpolar solvent. For determination, several instruments are supercritical carbon dioxide at a flow rate of 3 ml/min and a premix is essential, since a deficiency of this vitamin will result in suitable. Among official methods, colorimetric detection and sample backpressure of 146 bar. Detection for ppm level samples is with Diode adverse health effects in the animal, yet an overabundance of the titrations are used to determine the content of pure materials. AOAC Array using a wavelength of 260 nm. Trace level samples are compound can be toxic. A method was developed and validated 974.30 stipulates the use of Gas Chromatography with flame ionization quantitated using Tandem Mass Spectrometry (Agilent 6490, APCI utilizing Supercritical Fluid Chromatography with Diode Array or for the analysis of premixes. Other published methods utilize normal source) with a quantifier transition of 173.1/105 da. Ionization effects Tandem Mass Spectrometer detection for the resolution and analysis of and reverse phase High Performance Liquid Chromatography with UV are compensated for with stable isotope internal standard dilution Figure 4. Menadione by SFC-MSMS, 150 ng/ml calibration standard. Menadione in animal feed premixes. This method has a rapid extraction wavelength detection, Fluorescence detection with post column (Menadione-[d8]) with a transition of 181.1/108.9 da. The injection cycle procedure requiring minimal analyst labor and quick chromatography, reduction and tandem Mass Spectrometry detection. time is 4.5 minutes. with Menadione resolved in less than 3 minutes. As new methodology for the analysis of Menadione was considered, For the method validation exercise, calibration ranges were established several attributes were desired. First, the method must be fit for at 1-30 mcg/ml for SFC-DAD and 10-300 ng/mL for SFC-MSMS. The purpose for the analysis of feed premixes in a wide concentration precision of the assay was determined by analyzing multiple replicates of Introduction range. Also, the method should be quick and uncomplicated to perform. samples with known concentration of Menadione over several days. Vitamin K3, or Menadione, is a synthetic form of Vitamin K, which is Finally, the method should minimize the use of expensive, toxic and Finally, the accuracy of the method was investigated through recovery widely used in the supplementation of animal feeds. It is the simplest environmentally hazardous solvents. To satisfy these requirements, studies of blank material fortified with known amounts of Menadione form of Vitamin K, possessing the 2-methyl-1, 4 napthoquinone Supercritical Fluid Chromatography was investigated. Sodium Bisulfite. Method performance criteria stipulated by AOAC structure common to all the K vitamins, but lacking the derivative In Supercritical Fluid Chromatography, a gas – universally carbon guidelines for precision and accuracy were achieved with this application. carbon side chain present on Vitamin K1 and K2. Menadione may be dioxide – is manipulated to its supercritical state through the adjustment modified by reacting with Sodium Bisulfite, creating Menadione Sodium of temperature and pressure. Under these conditions, the gas exhibits Table 1. Assay Precision Bisulfite and other related structures. This modification results in a properties of a solvent, but with a much lower viscosity than a liquid. stable, inexpensive, and water soluble form of Vitamin K which is Menadione This supercritical fluid is used as the major component of the Menadione expected expected range Average Determined conducive to feed supplementation. chromatographic mobile phase. The low viscosity allows the content (mcg/g) (mcg/g) Instrument N Amount (mcg/g) RSD% supercritical fluid to be pumped at dramatically faster flow rates than 593 445-741 9 556 5.0 Figure 5. Menadione calibration curve, SFC-DAD. liquid chromatography, creating very quick injection cycle times. 3100 2325-3875 SFC-DAD 9 2834 3.6 NA NA 9 12.4 4.5 NA NA SFC-MSMS 9 12.9 6.2 Conclusion A method for the analysis of Menadione has been developed and Table 2. Assay Accuracy validated using SFC-DAD and SFC-MSMS as a detection platform. The Fortification level (ppm) Analysis Instrument Average Recovery % use of Supercritical Fluid Chromatography presents several benefits. Pressure Analysis time is rapid at 4.5 minutes per injection. Solvent usage is 0.2 101.5 minimized, with only 1 ml of methanol waste produced per injection as 10 SFC-MSMS 104.0 a portion of the mobile phase. The remainder of the mobile phase is 60 103.0 carbon dioxide, which is inexpensive and requires no labor or expense 10 100.8 for disposal. Menadione is clearly resolved from interferences in 160 SFC-DAD 97.9 Figure 1. Menadione fortified samples by the stationary phase; trace level samples can easily 4000 101.6 be analyzed by SFC-MSMS. Unlike reverse phase HPLC methods, the hexane sample extract can be injected directly on the SFC column. This use of SFC-DAD and SFC-MSMS provides an accurate, quick mAU 17.5 Ch1 260nm,1nm and uncomplicated method to analyze a range of Menadione in animal feed premixes. 15.0 Temperature 12.5 10.0 Sample Extraction 7.5 A representative portion of feed premix is prepared by cryo-milling. A 5.0 suitable aliquot of sample is collected in a disposable centrifuge flask, combined with a weak acid and vigourously agitated with a Genogrinder 2.5 Figure 2. Menadione Sodium Bisulfite (SPEX Sample Prep). Aliquotes of an aqeous basic solution and hexane 0.0 are subsequantly added to the flask, which is again processed on the Genogrinder. The sample tubes are briefly centrifuged, and an aliquot of 1.50 1.75 2.00 2.25 2.50 2.75 3.00 the upper Hexane phase is collected for analysis. Figure 3. Menadione by SFC-DAD. Sample containing 160 ppm Menadione. Presented at the AOAC Annual Meeting and Exposition 2019.
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