Lecture №7
Vitamins as medicines: general
characteristic, methods of obtaining,
classification, analysis, storage,
precondition of their usage in medical
practice. Vitamins of the aliphatic and
aromatic rows.
prepared ass. Medvid I.I.,
ass. Kozachok S.S.
Vitamins - are organic compounds of
different chemical structures, which in small
amounts required for the normal organism living.
They are a part of enzyme systems, which are
biological catalysts of the chemical reactions in
living cells and are involved in metabolism. The
human and animals can not synthesize vitamins or
synthesize them in insufficient quantities (nicotinic
acid) and therefore must obtain them from food. In
some cases vitamins are formed in the tissues as a
result of chemical transformation of substances
that are their precursors (provitamins).
In 1912 y. polish scientist K. Funk proposed
term “vitamins” that means “amines necessary for
life”.
Classification of vitamins
1. By the solubility:
• fat soluble (A, D, E, F, K )
• Water-soluble (group В, С, synthetic analogs of
2.
•
•
3.
К, РР, Р)
By letters:
by the disease that occurs at the insufficient
amount of this vitamin (С – scurvy
(antiscorbutic), А –antixerophthalmic, В – beriberi, Е – one that ensures procreation.
additional figures at the expanding of the group
of vitamins (В1 – В15, Вс)
Chemical classification.
Chemical classification of vitamins
I.
Vitamins of the aliphatic row:
а) Derivatives of the unsaturated polyoxy-- lactones (ascorbic acid
(vitamin C));
b) Derivatives of gluconic acid esters (pangamic acid (vitamin В15));
c) Derivatives of - aminoacids (pantothenic acid (vitamin В3)).
II. Vitamins of the alicyclic row:
а) cyclohexyl isoprenoids(retinols (vitamins of A group));
b) Cyclohexanolethylenehydrindanoic (calciferols (vitamins of group
D)).
III. Vitamins of the aromatic row (naphthoquinone derivatives):
c) natural vitamins of К group (phylloquinone– К1, menaquinone – К2);
d) synthetic analogues of vitamins of К group (menadione, vikasol).
IV. Vitamins of the heterocyclic row:
1) Chromane derivatives
а) tocopherols (vitamins of Е group);
b) bioflavonoids (vitamins of Р group).
2) Pyridine derivatives
а) nicotinic acid and its amide (vitamine of РР group);
b) oxymethylpyridine vitamines (vitamins of В6 group).
3) pyrimidine derivatives (thiamin (vitamin В1).
4) Pterine derivatives (folic acid (vitamin Вс).
5) Isoalloxazine derivatives or flavin vitamins (riboflavin
(vitamin В2))
6) Corrine derivatives – cobalamins (vitamins of В12 group).
Obtaining of vitamins
• Synthetic and semi-synthetic methods (С, А, Е, D, В1, В2, РР
and others).
• From plant and animal raw materials , microorganisms (С fruit-bloom, Р –waste of the tea industry, D –natural sterines,
А –fish oil, Е –vegetable fats, В12 –product of
microbiological synthesis of antibiotics, effluents).
Properties
White crystals or crystalline powder (rutin - a
green- yellow, folic acid - a yellow or yelloworange,
riboflavin
yellow-orange,
cyanocobalamin - dark red). Tocopherol acetatelight yellow, transparent, dense, oily liquid with
slight odor.
Vitamins are unstable under the action of light, air
and heat (some of them).
Identification of vitamins
• There are not general reactions, except nitrogen
determination by the Kjeldahl method.
• Often the group reaction(on the pyridine cycle etc.)
• More often - reactions that depend on the individual
characteristics of the chemical structure.
• According to the SPhU requirements – 10
preparations (D, С, РР, nicotinamide В6, В2, В1
(hydrobromide), В1 (hydrochloride), Вс, В12:
ІR-, UV- spectroscopy, chromatography.
Assay of vitamins
• Biological methods - determining of the biological
activity of vitamins. Studies conducted on rats,
pigeons, guinea pigs, which are moved on a diet
(exclude the study vitamin from the food). Then
determines which of the study vitamin can cure or
save the animal from avitaminosis. Parallel conduct
similar studies with the standard drug. Activity in IU
(international unit) - the notional amount of the
standard drug in mg or mcg (). For one unit is
considered to be the minimum amount of vitamin
that cures or prevents the animal from avitaminosis.
1 IU is different in different vitamins (1 IU of
vitamin A corresponds to 0,344 g of tocopherol
acetate, vitamin D - 0,25 g of ergocalciferol).
• Currently, the most frequently for quantification use
physical, physico-chemical and chemical methods.
USAGE
• Parts of biocatalysts (enzymes) that cause different
functions in the body metabolism. Hypo-and
avitaminosis of the some vitamin. In addition,
vitamins of В group –CNS diseases, heart diseases;
В12 – anemia; РР – a violation of the peripheral
circulation; Е – for the pregnancy keeping; D –
rachitis; А – skin and eye disease. Multivitamins–
support during the cold season, reduce the risk of
heart diseases and others.
• Side effects - allergic reactions (Multi-tabs, Kinderbiovital), dyspeptic disorders. Supervitaminosis –
vitamines А, D, К; essentiale Н (vitamins of
Вgroup) – at the expense of long reception.
Vitamins of the aliphatic row
• Ascorbic acid belongs to the derivatives of polyoxy-γ-
•
•
lactones of the unsaturated carboxylic acids, On the other
hand it can be attributed to the vitamins of heterocyclic
series as furan derivative. It is widely distributed in nature.
Especially rich in it is flora: fresh vegetables, fruits, etc. In
industry, ascorbic acid synthesized from D-glucose.
To the vitamins ofaliphatic row, derivatives of gluconic
acid esters, pangamic acid belongs (vitamin В15). In
medical practice is used its calcium salt. Pangamic acid is
a part of the rice bran, yeast, blood, liver.
To the vitamins ofaliphatic row, dertivatives of βaminoacids, pantothenic acid belongs. Yeast, eggs, liver
and egg yolk are rich on pentothenic acid. In medical
practice is used its calcium salt.
Ascorbic acid (Acidum ascorbicum)
Vitamin С (SPhU)
CH2OH
H
OH
O
O
OH
OH
(R)-5-[(S)-1,2- Dihydroxyethyl]-3,4-dihydroxy-5Hfuran-2-on
 -lactone-2,3-dehydro-L-gulonic acid
Extraction of ascorbic acid
Available in fresh vegetables - cabbage, beets, lettuce, tomatoes,
potatoes, berries - strawberries, currents, fruits - lemon, orange. t is
also found in milk, eggs, rose hips, fennel, etc.. For the extraction of
ascorbic acid from the rose hips produced water extract, which
is thickened in vacuum to the thicken of syrup. From the
remainder precipitated ballast substances with alcohol and ether, and
the filtrate evaporated to the dry state. Residue is clearing by
crystallization or chromatographic method.
The basic amount of ascorbic acid is now extracted synthetically,
based on D-glucose, that can be transformed by the reduction in the
D-sorbitol and D-sorbitol by enzymatic oxidation - in the L-sorbose
To protect the alcohol group of sorbose, at first it is condensed with
two molecules of acetone, and then oxidize diacetone sorbose by
КMnO4. Obtained diacetone ketoglutaric acid is saponificated to
ketogulonic acid.
Properties of ascorbic acid
• White or almost white crystalline powder of or
colorless crystals that change color under the
action of air and moisture. Easily soluble in water,
soluble in 96% alcohol, practically indissoluble in
ether. Melts at about 190 ° C with decomposition.
• By endiol group ascorbic acid shows both acidic
and restorative properties.
• Acidic nature is cased by the mobility of hydrogen
atom in hydroxyl group in position 3; at the alkali
titration ascorbic acid behaves like a monobasic
acid.
Ascorbic acid oxidizes in two stages :
1. reversible oxidation to dehydroascorbic acid
(keto-form);
2. irreversible process of oxidation, which leads
to the formation of furfural:
CH2OH
CH2OH
H
H
OH
O
OH
O
OH
[O]
OH
O
[O]
O
[H]
O
O
C
H
O
O
Identification of ascorbic acid
1. By the physico-chemical constants : UV- and IRspectroscopy, determination of рН and the specific optical
rotation.
2. Add to the solution of ascorbic acid diluted nitrate acid
and silver nitrate solution – silver gray metallic
precipitate falls:
CH2OH
H
OH
CH2OH
H
O
OH
O
O + 2AgNO3
OH
OH
+
2Ag
+
O
2HNO3
O
O
+
3. Unpharmacopoeial reactions:
a) To 1 ml of obtained solution add 2 drops of iron (III)
chloride R2 solution and after1 min. 1 drop of of
potassium ferricyanide R; blue color appeares:
CH2OH
H
OH
CH2OH
H
O
OH
O
O + 2FeCl3
O
OH
OH
+
2FeCl2 +
O
O
3FeCl2 + 2K3[Fe(CN)6] → Fe3[Fe(CN)6]2 + 6KCl.
To 1 ml of obtained solution add 5-7 drops of 0,05 М iodine
solution; solution becomes transparent:
b)
CH2OH
CH2OH
H
OH
H
O
OH
O
O + 2HI
O + I2
OH
OH
O
O
2HCl ;
c)
To 1 ml of obtained solution add 1 drop of CuSO4 solution and 2-3
drops of 1 % NH4CNS solution; white precipitate forms:
CH2OH
H
CH2OH
OH
H
O
OH
O
O
+ 2CuSO4 + 2NH4CNS
+
OH
OH
+
d)
O
2CuCNS
O
O
+
(NH4)2SO4
H2SO4
+
To the aqueous solution of the preparation add NaHCO3 and FeSO4,
shake and leave to stand; a dark purple color appears which
disappears at the adding of H2SO4 dil.:
CH2OH
H
OH
O
Na2SO4 + 2CO2
O + FeSO4 + 2NaHCO3
2
OH
CH2OH
OH
H
OH
O
+
Fe
O
O-
OH
2
+ 2H2O +
e)
at the adding by drops 2,6dichlorophenolinedophenolate solution to the
solution of ascorbic acid blue color disappears:
f)
•
•
Ascorbic acid is easily oxidized at the interaction with :
Phosphoric-molybdenum acid (the products of blue color
form);
methylene blue (discoloration occurs due to formation of
leucobase);
Potassium permanganate(discoloration;
•
Fehling reagent (red color)
•
Assay of ascorbic acid
Iodometry, direct titration (SPhU). Indicator – starch. E m .=
М. m./2
CH2OH
CH2OH
H
OH
H
O
OH
O
O + 2HI .
O + I2
OH
OH
O
O
Alkalimetry, direct titration . Indicator – phenolphthalein).
E.m. = М. m.
CH2OH
CH2OH
H
OH
H
O
OH
O
O + H2O .
O + NaOH
OH
OH
ONa
OH
• Iodatometry, direct titration in acidic medium in the
presence of potassium iodide, indicator – starch. At the
point of equivalence excess of potassium iodate causes the
blue color of solution. E.m. = М. m./2.
• Titration by sodium 2,6-dichlorophenolindophenolate
solution (for the determination of ascorbic acid in row
material). E.m. = М. m./2
• Other redox methods (Iodochlorometry, cerimetry and
others).
Ascorbic acid storage
• In nonmetallic airtight containers, in the dark place.
Usage of ascorbic acid
• Takes part in oxidative-reduction processes, in
carbohydrates metabolism and tissue regeneration,
the formation of steroid hormones. Daily demand of
a healthy person - 80-100 mg.
• In preventive and therapeutic purposes at the
scorbutus (scurvy), bleeding of various etiologies,
infectious diseases and poisonings, liver and kidneys
diseases.
• Issue: tablets, dragee by 0,025; 0,05; 0,1; 0,5 g; 5%
and 10% solutions for injections. Soluble tablets by
1,0 g.
Calcium pangamate
(Calcii pangamas), vit. В15, Kalham
By the chemical structure pangamic acid is an ester of Dgluconic and dimethylaminoacetic acids (dimethylglycine).
Substance, except for calcium pangamate contains calcium
gluconate (25%) and calcium chloride (6%).
Extraction of pangamic acid
• Isolated from rice bran, yeast, blood, liver.
• Synthesized from D-glucose:
• Properties. White, sometimes yellowish crystalline
powder with characteristic odor. Hygroscopic. Easily
soluble in water and hardly soluble in organic solvents.
Identification of calcium pangamate
• By the physico-chemical constants: IR spectroscopy.
• Substance gives reactions on calcium (4
•
pharmacopoeial reaction).
Residue of gluconic is confirmed by the reaction with
iron (III) salts by the formation of light green color.
• Alkaline hydrolysis. After the heating of substance
•
with solution of sodium hydroxide smell of amines
appears.
The reaction of formation of colored iron hydroxamate
(esteric group):
Assay of calcium pengamate
• Given that the substance except calcium
1.
2.
3.
4.
pangamate, also includes calcium gluconate and
calcium chloride, quantitatively determine the
content of:
Nitrogen (3,6 - 4,2%) - acidimetry in nonaqueous medium;
Calcium (5,8 - 7,4%) – complexonometry
method;
Chlorides (not more than 2,2%) - a method of
reverse argentometry by Folgard;
The amount of carboxyl groups (11 - 15%) - by
ion exchange chromatography.
STORAGE
• In glass airtight containers, in a dry place.
Usage of calcium pangamate
• Activates the transfer of oxygen to the cells of tissues
•
and takes part in the methylation of biosubstrates,
improves lipid metabolism.
Similar to vitamins preparation. Calcium pangamate
is used for the treatment of various forms of
atherosclerosis, cirrhosis, alcoholism and other
diseases.
• Issue : tablets by 0,05 g.
Calcium pantothenate
(Calcii pantothenas), vit. В3
Calcium salt of D-(+)-α,γ-dioxy-β,β-dimethylbutyryl-Namide-β'-aminopropionic acid (β-alanine).
Properties. White fine crystalline powder without smell.
Easily soluble in water, very little soluble in organic
solvents.
Extraction of calcium
pantothenate
• In large quantities contained in caviar, yeast,
liver, egg yolk, rice.
• Synthetically is extracted by the following
scheme:
Identification of calcium pantothenate
1. By the physico-chemical constants: the specific
rotation from +25 to +28° (5 % aqueous solution)
2. Substance gives reactions on calcium.
3. With the solution of copper (II) sulfate in an
alkaline medium substance forms a blue complex
(β-alanine):
4. Residue of α,γ -dioxy- β,β –dimethylbutyric acid
determine after alkaline hydrolysis. . Substance is boiled
with sodium hydroxide solution, after cooling acidified by
acid chloride solution and added iron (III) chloride yellow color appears:
5. The reaction of colored iron hydroxamate
formation : γ-butyrolactone
Assay of calcium pantothenate
Determine the content of:
 Nitrogen (5,7 – 6,0%) – Kjeldahl method;
 Calcium (8,2 – 8,6%) - complexonometry method.
Test on purity
Specific impurity. Pantoyl lactone –is determined
spectrophotometricaly in the visible part of the
spectrum by the reaction of iron hydroxammate
formation.
Storage
• In glass airtight containers, in a dry place at the room
temperature.
Usage of calcium pantothenate
• Participates in hydrocarbon and fat metabolism,
•
•
•
stimulates the formation of corticosteroids and is part
of coenzyme A.
The daily demand - 10-12 mg. Since it is formed
during the vital functions of Escherichia coli, its
avitaminosis is not observed.
To treat neuralgia, eczema, allergies, polyneuritis, and
other diseases related with violation of metabolism
and at the inflammatory processes.
Issue: tablets by 0,1 g.
Vitamins of the alicyclic row
• Vitamins of the alyciclic row include retinols (vitamins of А group)
•
•
•
•
and calciferols (vitamins of D group).
In the core of the retinol molecule is trimethylcyclohexanoic cycle
associated with tetraenol conjugate chain, in the end of which is
hydroxyl or aldehyde group. Retinol was obtained from the liver of
fish in 1909 year. In 1928 y., Euler found that some plants are
substances that have provitamin activity, scilicet are the precursors of
vitamins. Provitamins of vitamin A are α-, β-and γ-carotene.
. To vitamins of D group, which is called calciferols or antirachitis
include derivatives of cyclohexanol ethylene-hydrindane. Is opened
few vitamins of D group: D1-D7 similar by the chemical structure,
physico-chemical properties and pharmacological action. The
practical usage hame the following vitamins: vitamin D2
(ergocalciferol) and vitamin D3 (cholecalciferol).
Vitamins D2 and D3 are in egg yolks, caviar, butter, milk. A
significant number of them accompanied by retinol in liver and
adipose tissue of fish and marine animals.
In medicine is used retinol acetate and ergocalciferol.
Retinol acetate
(Retinoli acetas) vit. А
Trans-9,13-Dimethyl-7-( 1,1,5-trimethylcyclohexene5-yl-6)nonatatraene-7,9,11,13-ol-15 acetate
Extraction of retinol
Hydrolysis of fish liver by 15 % КОН solution in the
atmosphere of inert gas is used for the vitamin A
obtaining.
Main quantity of vitamin A is obtained synthetically
from citral by the following scheme: β-ionone
Properties of the retinol acetate
White or pale yellow crystals with a weak odor.
Extremely unstable under the action of air oxygen
and light (easily oxidizes by the atmospheric oxygen,
especially at elevated temperatures and light, with
the formation of heronic acid). Practically insoluble in
water, soluble in 95% alcohol, chloroform, ether and
oils.
Identification of retinol acetate
1. The reaction with antimony (III) chloride in
2.
3.
chloroform environment - blue color appears.
The reaction with aluminum chloride - blue color
appears.
Reactions on the unsaturated bonds (discoloration of
iodine, bromine water, reduction of
phosphorwolframic acid, AuCl3).
Assay of retinol acetate
• UV-spectrophotometry
• Photocolorimetry by the reaction with SbCl3
Storige of retinol acetate
Due to the fact that the substance is easily oxidizes,
store it in sealed ampoules in a stream of nitrogen,
which keep from the action of light, at the
temperatures no more than +5°. Oil solutions of
retinol acetate are stored in chock-filled, well
corked cups of dark glasses at the temperatures no
more than +10 °С.
Usage of retinol acetate
• In the treatment of avitaminosis, diseases and lesions of the
•
•
•
•
•
skin, eye diseases. Prescribed as pills, granules, oil solutions
orally, intramuscularly and topically. During the treatment is
necessary to consider the possibility of hypervitaminosis.
Daily dose for a healthy person - 1 mg treatment dose - up
to 10 mg (33000 UA), but not more than 30 mg (100 000
UA).
1 IU = 0,344 microgram or 100000 IU = 0,0344 g of retinol
acetate.
There are two forms of retinol: acetate and palmytate (more
stable then acetate).
Issue. VitaminА gel. caps. By 2500, 8000, 12000, 50000,
100000 IU.
Caps. Aevit – vit. А + Е – caps. №24 (retinol 30000 IU,
tocopherol 70 IU).
Vit. A are carotenes, which contained in fruits, carrots,
red peppers and others. -Carotene in the human
body decomposes under the influence of liver
enzymes into two molecules of vitamin А, - and carotenes form only one molecule of vitamin А.β α γ
Ergocalciferol (Ergocalciferolum),
vit. D2 (SPhU)
(5Z,7E,22E)-9,10-Secoergosta-5,7,10(19),22-tetraene-3β-ol
Cyclopentanophenantrene
General formula of calciferols
Extraction of ergocalciferol
Vitamin D2 by its structure is similar to steroids. This
vitamin is obtained by the UV-radiation of ergosterine,
which contains in yeast, the uterine horn etc.. Process of
ergosterine transformation in ergocalciferol conducts
through the formation of lumisterine and tachysterine:
Properties of ergocalciferol
• White or slightly yellowish crystalline powder or
white or almost white crystals. Practically insoluble
in water, easily soluble in 96%alcohol, soluble in
fatty oils. Sensitive to air, heat and light. Solutions
in volatile solvents are volatile and must been used
immediately after preparation. In the solutions is
possible the depending on temperature and time
reversible isomerization in pre-ergocalciferol.
Activity of the substance is caused by both
components.
• Solution of ergocalciferol in oil - is a transparent
oily liquid from light yellow to dark yellow.
Identification of ergocalciferol
1. By the physico-chemical constants : IR-spectroscopy.
2. Steroid part of molecule cases Liberman reaction
3.
4.
5.
(chloroform solution of the drug at the shaking with acetic
anhydride and sulfate acid becomes red, color transforms
to purple, then to blue and finally to green).
At the interaction with antimony (III) chloride solution in
the presence of acetylchloride formed orange-pink color.
This reaction is also used for determination of impurities
by TLC and assay by the photocolorimetry method.
Sobel-Meyer’s reaction (with glycerin-1 ,3-dichlohydrine)
- green coloration.
Shaltegger’s reaction (drug is boiled with benzene
solutions of aldehydes (vanillin, furfural, anisic, etc.),then
add perchlorate acid) - red color appears.
Assay fo ergocalciferol
• Liquid chromatography (SPhU).
• Photocolorimetry
Storage of ergocalciferol
Ergocalciferol is stored in an airtight container
under nitrogen in a dark place at a temperature from
2 °С to 8 °С. The contents of opened containers
should be used immediately. Medical forms of
ergocalciferol are stored in chock-filled, well corked
cups of dark glasses, because it easily oxidizes by
the air oxygen, under the action of light gradually
decomposes and forms toxic products.
Cholecalciferol
(Cholecalciferolum), vit. D3
(5Z,7E)-9,10-Secocholesta-5,7,10(19)-triene-3β-ol
At first was obtained from fish oil. Provitamin of vitamin D3 is 7dihydrocholesterol
Because of the presence of cholesterol and 7-dehydrocholesterol
in the humane skin lipids content it is possible to synthesize vitamin
D3 under the action of sun radiation or UV-radiation on the surface of
the humane body.
Usage of calciferols
• In the medical practice use alcoholic (0,5 %) and oil
(0,125 %) solutions of vitamin D2 to prevent and
treat rachitis, but also at the bone diseases associated
with violations of calcium metabolism. Vitamins of
D group are effective for treatment of all forms of
erythematosus and other skin diseases.
• Daily demand for a healthy man– 1000 IU.
• Vitamin D3 – cholecalciferol. Tablets Videine (2000
іand5000 IU). Vit. А+D3 – aqueous solution bottles
by 10 ml.
• Fish Oil.
Aromatic vitamins
• 2-methyl-1,4-naphthoquinone (vitamin of К group)
•
•
derivatives belong to the aromatic vitamin’s raw. They
have antihemorragic action and participate in the
formation of prothrombin.
Vitamin К1 (phylloquinone) present in the plants (lucerne ,
spinach , cabbage), vitamin К2 (pharnoquinone) is in
animal products and is produced by intestinal
microflora. Vitamin К3 (menadione) is called 2-methyl1,4-naphtoquinone.
In medical practice, using a synthetic analogue of
vitamin K - vikasol.
Coagulation effect of vitamin K is very specific, since the
small changes in their molecule lead to a significant change in
their activity. The discovery of Ansbaher and Ferngolts (1939)
was a great achievement, that the 2-methylnaphthoquinone (it
was called vitamin K3) is by three times more active than
vitamin K1. Insolubility in water of 3-methylnaphthoquinone has
led to the synthesis of a number of its water-soluble derivatives
(by O.V. Palladin), including vikasol.
Vikasol (Vikasolum)
(Menadione of sodium
bisulfite) O
CH3
SO3Na * 3 H2O
O
•
Sodium 2,3-dihydro-2-methyl-1,4-naphthoquinone-2-sulfonate
threehydrate
CHARACTERS. A pale-yellow, crystalline powder, freely
soluble in water, very slightly soluble in ether, hard soluble in
alcohol.
Vikasol obtaining
Precursor for the synthesis of the drug is a βmethylnaphthalene, which is extracted from the waste
cokecoal industry. Methylnaphthalene is oxidized in
acetate
acid
by
chromic
anhydride
to
methylnaphthoquinone, which is heated with an
aqueous solution of sodium hydrosulfite:
Identification reaction of vikasol is based on its lability in
alkaline and acid solutions.
Identification of vikasol
1. It gives reaction of a sodium.
2. At the interaction with a sodium hydroxide solution there is
settled down a yellow crystalline precipitate of 2-methyl-1 ,4naphthoquinone, which is extracted by chloroform, purified from
impurities and determine the melting point (104-107 ° C):
Sodium sulfite is determined after the removal of the excess
of alkali solution by a iodine solution according to the
iodine discoloration reaction. Vikasol itself does not react
with iodine.
Na2SO3 + I2 + H2O → Na2SO4 + 2HI
3. At the interaction of vikasol with a concentrated
sulfuric acid there is sulfurdioxide small:
4. Substance + ethanol + HCl conc.  red colour.
5. Aqua solution of the substance + sodium ethylate 
Red-brown color, according to the formation of 2-oxi-3-methylnaphthoquinone (phtyoxol).
Impurities
•
•
•
Sodium bisulfite and 2-methyl-1,4-naphthohydroquinone-3sulfonate are the specific impurities in vikasol.
Sodium bisulfite NaHSO3 is determined by iodometric titration
method (less than 2 %).
2-methyl-1,4-naphthohydroquinone-3-sulfonate is determined
by the adding of о-phenanthroline - hould not form the
precipitate (the impurity is not allowed.
Assay
1. Cerimetri. Direct titration, the indicator is o-phenanthroline.
By the interaction with a sodium hydroxide solution 2-methyl1 ,4-naphthoquinone is precipitated, which is extracted with
chloroform. After removal of chloroform, it is reduced in an
acidic medium to 2-methyl-1 ,4-dioxinaphthalene, then it is
titrated by a solution of cerium (IV) sulfate until the green
color:
2. Gravimetry. (Precipitation form – 2-methyl-1,4naphthoquinone).
Storage
• Store protected from light.
Application
To increase the clotting of blood at various
bleedings. Water-soluble synthetic substitute of
K group vitamins, which take part in the
formation of liver prothrombin and promotes the
normal blood coagulation. At Haemophilia it
does not act. It acts during 12-18 hours after
injection.
Produced: powder, tablets. оn 0,015 g, 1% solution for
injection.
• Per oral: the highest day dose – 60 mg, intra/muscular
– 30 mg.
Thank you for
attention!