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Pharmacological Properties of Vitamin K3 (Menadione)

View: 68 Author: Site Editor Publish Time: 2022-04-08 Origin: site

Vitamin K3, also known as Menadione, is an organic compound with the chemical formula C11H8O2 and is clinically used as a procoagulant for the treatment of bleeding disorders caused by vitamin K deficiency, such as neonatal haemorrhage, vitamin K deficiency due to intestinal malabsorption and hypoprothrombinemia. It is not naturally occurring and is not a vitamin in itself. Instead, it is a fat-soluble initial form that is converted to vitamin K in the liver. Menadione is also known as vitaminogen.


Vitamin K is required for normal body function and its main role is to control blood clots. Specifically, vitamin K is responsible for the production of the blood clotting agent thrombin. In addition, this vitamin plays an important role in the regulation of bone calcification.


In plants, this vitamin is used as an electron acceptor for the process of photosynthesis. Vitamin K accepts electrons when chlorophyll is in a stimulated state. This allows chlorophyll to release non-photochemical energy as it shifts to a lower energy state. Plant respiration is dependent on an adequate supply of vitamin K.


Basic information.

Chemical formula: C11H8O2

Molecular weight: 172.18

CAS No.: 58027-5

EINECS number: 200-372-6


Physical and chemical properties.

Density: 1.225g/cm3

Melting point: 105-107°C

Boiling point: 304.5°C

Flash point: 113.8°C

logP: 2.0119

Appearance: Yellow crystalline powder


Molecular structure data.

Molar refractive index: 47.60

Molar volume (cm3/mol): 140.5

Isotropic specific volume (90.2K): 366.8

Surface tension (dyne/cm): 46.4

Polarisation rate (10-24cm3): 18.87


Calculated chemical data.

Reference value for calculation of hydrophobic parameters (XlogP): none

Number of hydrogen bond donors: 0

Number of hydrogen-bonded receptors: 2

Number of rotatable chemical bonds: 0

Number of mutant isomers: 3

Topological molecular polar surface area: 34.1

Number of heavy atoms: 13

Surface charge: 0

Complexity: 289

Number of isotope atoms: 0

Determine the number of atomic structure centres: 0

Indeterminate number of atomic structure centres: 0

Determine the number of bonding centres: 0

Uncertain number of bonding centres: 0

Number of covalent bonding units: 1


Functional efficacy.

A vitamin supplement. Vitamin K is essential for the synthesis of proenzyme (factor B) in the liver and is involved in the synthesis of coagulation factors VII, IX and X, which maintain the physiological process of blood clotting in animals. Deficiency of vitamin K can lead to impaired synthesis of these coagulation factors, affecting the coagulation process and causing bleeding. Vitamin K is also required for the vitamin K-dependent carboxylation system in the animal organism (mainly in tissues and organs such as the liver, bones, testes, skin and kidneys) and is an indispensable factor in the synthesis of skeletal proteins (BGP). In addition, it plays an important role in the metabolism of high-energy compounds and oxidative phosphorylation, as well as in aspects of metabolism with other fat-soluble vitamins, and has diuretic and hepatic detoxification enhancing functions, participating in the structure of membranes and lowering blood pressure.



1. There is a risk of allergic reactions to vitamin K.

2. When severe bleeding occurs due to vitamin K-dependent factor deficiency, short-term application is often insufficient for immediate effect and may be preceded by intravenous infusion of prothrombin complex, plasma or fresh blood.

3. When used to correct oral anticoagulant-induced hypoprothrombinemia, the minimum effective dose should be tried first and adjusted by prothrombin time measurement; excessive vitamin K may make subsequent continuous anticoagulation difficult.

4. Bleeding in patients with cirrhosis or advanced liver disease, as well as bleeding due to heparin is not effective with sodium bisulfite Menadione injection.


Usage and Dosage

1. Haemostasis: Intramuscular injection 2-4mg each time, 4-8mg a day; Give intramuscular injection to pregnant women 1 week before delivery, 2-4mg a day to prevent haemorrhage in newborns.

2. Antispasmodic and analgesic: Intramuscular injection, 8-16mg each time.

Paediatric use: Larger doses of vitamin K3 can cause haemolytic anaemia, hyperbilirubinemia and nuclear jaundice in newborns, especially premature babies, but vitamin K1 is less common.



Sodium bisulfite methenamine injection is a vitamin drug. Vitamin k is essential for the synthesis of factors II, VII, IX and X by the liver. Vitamin k deficiency can cause impaired or abnormal synthesis of these coagulation factors, which can be seen clinically as bleeding tendency and prolonged prothrombin time.


After absorption by intramuscular injection, it is transported with β-lipoproteins and it takes about 8-24 hours for the effects to become apparent and to be utilised in the liver, taking several days to restore prothrombin to normal levels and will be excreted as glucuronide and sulphate conjugate via the kidney and biliary tract.

Adverse reactions

1. Localised redness, swelling and pain are visible.

2. Higher doses may cause haemolytic anaemia, hyperbilirubinemia and jaundice in newborns and premature infants. In patients with erythrocyte 6-phosphate dehydrogenase deficiency, acute haemolytic anaemia may be induced.

3. High doses can cause liver damage. Patients with hepatic insufficiency may be switched to vitamin K1.


1. Oral anticoagulants such as bicoumarins can interfere with vitamin K metabolism, and the two drugs used together can counteract each other's effects.

2. Larger doses of salicylates, sulphonamides, quinine and quinidine can also affect the vitamin K effect.


Determination of vitamin K3.


In a weakly alkaline medium at pH 8.7-9.5, vitamin K3 (VK3) is able to discolour methyl green with a maximum discolouration wavelength of 630 nm and two new absorption peaks in the UV region. The degree of discolouration (ΔA) is proportional to the VK3 concentration in the range of 0.11-2.40 mg/L and could be used for the spectrophotometric determination of VK3. The method has high sensitivity with an apparent molar absorbance coefficient ε630 = 2.13 x 105L-mol-1-cm-1 and a detection limit (3σ) of 32.0 μg/L for VK3. The method has good selectivity and can be used for the determination of VK3 in certain pharmaceutical preparations and blood drugs.

Extraction spectrophotometry

The reaction of vitamin K3 (VK3) with the basic dyes butyl rhodamine B (BRB), ethyl violet (EV) and methylene blue (MB) to form ion-pair conjugates is investigated and the optimum conditions for the reaction are determined. A simple, rapid, selective and sensitive analytical method is  developed for the determination of VK3, which reacted with BRB, EV and MB to form ion-pair

associated matter extractable by organic solvents. The maximum absorption of ion-pair

associated matter is observed at 568, 613 and 658nm, and the apparent molar coefficients are 2.92×104, 6.96×104 and 4.85×104L·mol-1·cm-1, respectively. The compositions of

associated matter are 1:1, and the stability constants are 9.5×105, 1.9×106 and 7.8×105, respectively. The drug concentrations in the range of 0.0083 ~ 13, 0.029 ~ 6.6 and 0.015 ~ 9.6 mg/L are in accordance with Beer's law. The recovery rates is 96% ~ 103%. The method can be successfully used for the determination of VK3 content in pharmaceutical preparations.

Gas Chromatography

Multivitamin complex additives or premix feeds contain more vitamin E and vitamin K3, of which vitamin E is mainly present in its acetate form due to its easy oxidation. For the determination of vitamin E acetate content, usually using high performance liquid phase method, or colorimetric method, fluorescence method, etc., the samples need to be saponified, extracted, washed, concentrated and pre-treated. The operation is cumbersome, long, in the production process can not monitor the quality of the product in a timely manner.

Preparation method.

Preparation of vitamin K3: obtained by oxidation and addition of o-methylnaphthoquinone as raw material.

Oxidation of methyl naphthalene with chromic anhydride

Dissolve 2-methylnaphthalene in glacial acetic acid, stir and cool to below 40℃, slowly add the mixture of chromic anhydride and equal amount of water to maintain the temperature at 35-40℃. After addition, keep it at 40℃ for 0.5h, then increase the temperature to 70℃ for 45min, then increase the temperature to 85℃ for 15min, pour the reaction product into a large amount of water and precipitate 2-methylnaphthoquinone with constant stirring. The filter cake is washed repeatedly with water until the aqueous solution is acid-free and filtered dry to obtain 2-methylnaphthoquinone. The yield is 51%. 2-Methylnaphthalene can also be oxidized with sodium dichromate and potassium dichromate with approximately the same yield.

Chemically combined and then oxidised by chromic acid

2-Methylnaphthoquinone is obtained from the cyclisation of toluiquinone with butadiene, which is then oxidised by chromic acid. Toluiquinone is dissolved in glacial acetic acid and passed through butadiene to the required amount at below 20°C. After 20h of confinement and standing, the remaining butadiene is heated to escape and continued to be heated to about 110°C for 3h at reflux, then distilled under reduced pressure to recover about 30% of the glacial acetic acid. Then cool to below 40°C, slowly add a mixture of chromic acid and an equal amount of water to keep the temperature at 65-70°C. After addition, hold at 70-80°C for 1h to produce Menadione. [3]

Optimised process

Optimisation of the production process of vitamin K3. The optimized reaction conditions can be obtained by comparing the effects of the reaction raw material ratio, reaction temperature, reaction time and other factors on the product yield. Experiments shows that under the optimal process conditions (the substance ratio of 2-methyl-1,4-tetraquinone (2-MNQ) to NaHSO3 is 1:1.5; m(2-MNQ): V water/(g/mL) = 1.5; m(2-MNQ): V ethanol/(g/mL) = 4.0; the reaction temperature is 52~55℃; the reaction time is 1h), the yield of vitamin K3 is stable at more than 75%.