Riboflavin Sodium Phosphate CAS 130-40-5

Its stability under a range of pH conditions ensures that it retains its nutritional value even in processed foods.Beyond its energy-boosting benefits, it also supports healthy skin, eyes, and mucous membranes.

It is crucial for maintaining normal growth and development and is often recommended for individuals with deficiencies, which can manifest as skin disorders, eye fatigue, and slowed metabolism.

In the pharmaceutical industry, it is used to treat conditions associated with riboflavin deficiency, such as mouth sores, skin inflammation, and sensitivity to light.

It's also employed in some topical treatments due to its antioxidant properties and ability to help protect cells from damage.Overall, flavin mononucleotide is a versatile and essential nutrient that enhances the nutritional profile of foods and supplements, contributing to overall health and well-being. Its wide-ranging applications and stability make it a staple in both dietary formulations and medical interventions.

Industrial production is categorized into two core technical routes: conventional total chemical synthesis and enzyme-catalyzed biotransformation for high-grade pharmaceutical material, both starting with fermentation-refined riboflavin as the primary raw material.

The traditional chemical route employs phosphorus oxychloride as the phosphorylating agent in a pyridine–acetonitrile mixed solvent system under controlled temperature ranging from 30 °C to 36 °C, with a molar ratio of riboflavin to POCl₃ fixed at approximately 1:4.

The reaction is held isothermally for 2 hours to achieve site-specific phosphorylation at the 5'-hydroxyl of the ribitol moiety. Low-temperature hydrolysis eliminates phosphorylated byproduct impurities, followed by gradual neutralization with sodium hydroxide buffer to pH 4.5–5.2.

Crystallization proceeds under refrigerated static conditions and is further refined via recrystallization, delivering an overall yield of 72%–77%. This route is well-suited for food-grade bulk production, yet its key drawback lies in unavoidable formation of unwanted 4'-phosphate positional isomers, resulting in elevated downstream purification expenses.

High-purity injectable-grade material is manufactured via riboflavin kinase-mediated biocatalysis: high-purity riboflavin is obtained from Eremothecium ashbyii fermentation, then subjected to enzyme-specific 5'-selective phosphorylation within an ATP cofactor system with zero isomeric byproducts generated.

After neutralization, the feedstock is concentrated under reduced pressure and crystallized to meet compendial specifications of USP and EP pharmacopoeia.

Most domestic contemporary production adopts optimized low-temperature chemical phosphorylation supplemented with customized crystal seeds to regulate crystal particle size and cut residual organic solvent levels, striking a balance between manufacturing cost and finished product purity.

Currently, over 90% of pharmaceutical-grade sodium riboflavin phosphate is produced using either biocatalytic synthesis or optimized improved chemical protocols.

In 1879, British chemist Blyth isolated a yellow-green fluorescent substance termed lactoflavin from cow's milk whey, marking the origin of riboflavin research. Subsequent researchers across various countries extracted identical fluorescent fractions from egg yolk, animal liver and yeast, yet the chemical structure remained unidentified for decades.

In 1933, Kuhn's research team isolated trace pure riboflavin monomer from thousands of kilograms of fresh milk. The group finalized structural elucidation and accomplished total chemical synthesis of riboflavin in 1935, formally naming the compound Riboflavin and establishing the fundamental chemical backbone of vitamin B₂.

Parallel biochemical studies verified that endogenous biologically active vitamin B₂ exists predominantly as its 5'-phosphate ester (FMN), an essential coenzyme for flavoenzymes, which greatly accelerated the development of synthetic phosphorylated riboflavin derivatives.

Between 1938 and 1942, Roche Research Laboratories pioneered in vitro phosphorylation of riboflavin to produce riboflavin 5'-phosphate, which was neutralized with alkaline solution into its sodium salt, sodium riboflavin phosphate. This derivative exhibits markedly superior water solubility compared with free riboflavin, making it suitable for injectable pharmaceutical formulations.

Pilot-scale industrial manufacturing was realized across Europe and the United States in the 1950s; thanks to its outstanding aqueous solubility, it gradually replaced regular riboflavin in parenteral medicines.

The global expansion of feed and food industries throughout the 1970s prompted its inclusion as a legally permitted nutritional fortificant in national food standards.

Alongside the commercialization of fermentative riboflavin mass production, sodium riboflavin phosphate achieved widespread large-scale application, completing its full developmental path from endogenous natural biomolecule discovery to industrially manufactured active pharmaceutical ingredient.

A C18 alkylsilane-bonded silica chromatographic column is adopted. The mobile phase consists of phosphate buffer and methanol with gradient elution, and the detection wavelength is set at 374 nm.

Quantification is performed via the external standard method. For system suitability, the theoretical plate number calculated against sodium riboflavin phosphate for the principal peak shall be no less than 2000, enabling efficient separation of critical impurities including free riboflavin, 4'-phosphate positional isomer and polyphosphorylated byproducts.

The assay content of bulk drug is specified within the range of 96.0%–102.0%, and injection samples are diluted and assayed under identical chromatographic parameters.

Karl Fischer titration is used for water content determination to keep crystal water within regulatory limits. Residual organic solvents such as methanol and pyridine are quantified by gas chromatography (GC).

Heavy metals including lead, arsenic and cadmium are examined via atomic absorption spectrophotometry (AAS) or ICP-MS. Microbiological limits of injectable bulk materials are controlled in accordance with pharmacopoeial sterility test requirements. Combined application of above testing technologies fully complies with import and export inspection standards for pharmaceutical bulk drugs and finished medicinal preparations.