Extraction , Isolation and Structure Elucidation of Digoxin

Extraction , Isolation and Structure Elucidation
of Digoxin
Prepared By:
MOHAMMAD KHALID
(Assistant Professor)
Krishna Pharmacy College, Bijnor (UP)

content
Introduction
Mechanism of Action
Pharmacokinetics
Indication
Administration
Contraindication and Precaution
Use cautiously in
Adverse Effects
Extraction and Isolation of Digoxin
CHEMICAL TESTS
Structure Elucidation
09 May 2020 Krishna Pharmacy College, Bijnor 2

introduction
It is a purified cardiac glycoside extracted from the foxglove
plant, Digitalis lanata.
Its corresponding aglycone is digoxigenin, and its acetyl
derivative is acetyldigoxin.
It is widely used in the treatment of various heart conditions
namely atrial fibrillation, atrial flutter and sometimes heart
failure that cannot be controlled by other medication.
Pharmacological Class :- Cardiac Glycoside
Therapeutic Class :- Inotrope, antiarrhythmic
09 May 2020 Krishna Pharmacy College, Bijnor
3

Mechanism of Action
The main pharmacological effects of digoxin are on the heart.
It has mechanical effects as it increases myocardial contractility;
however, the duration of the contractile response is just slightly
increased.
Overall, the heart rate is decreased, while blood pressure
increases as the stroke volume is increased, leading to increased
tissue perfusion.
Myocardial efficiency is due to improved hemodynamics, and
the ventricular function curve is improved.

Continue....
Other, electrical effects are an initial brief increase
in action potential, followed by a decrease as the
K+ conductance increases due to an increased
intracellular amounts of Ca2+ ions.
The refractory period of the atria and ventricles is
decreased, while it increases in the sinoatrial and
AV nodes.
A less negative resting membrane potential is
made, leading to increased excitability

Continue....
Slight vasodilation is seen in heart failure. This
effect is contrary to effects that should be seen as a
result of increased intracellular calcium levels, but
this occurs since digoxin improves
hemodynamics, which leads to restored
angiotensin levels and decreased sympathetic
discharge, causing indirect vasodilation.
It also affects the kidney by increased renal blood
flow and increased glomerular filtration rate. A
mild diuretic effect is seen only in heart failure .

Pharmacokinetics
About 70 to 80% of an oral dose of digoxin is
absorbed, mainly in the proximal part of the small
intestine. The degree of binding to serum albumin
is 20 to 30%. Digoxin is extensively distributed in
the tissues, as reflected by the large volume of
distribution. High concentrations are found in the
heart and kidneys, but the skeletal muscles form
the largest digoxin storage.
The half-life of elimination varies between 26 and
45 hours

Continue....
The main route of elimination is renal excretion of
digoxin, which is closely correlated with the
glomerular filtration rate. In addition, some tubular
secretion and perhaps tubular reabsorption occurs.
Nearly all of the digoxin in the urine is excreted
unchanged, with a small part as active metabolites.
The clinical significance of dihydrodigoxin as a
metabolite remains to be resolved. About 25 to 28% of
digoxin is eliminated by nonrenal routes. Biliary
excretion may rise up to 30% of a given dose, but the
enterohepatic cycle seems to be of minor importance.

Indication
Heart Failure
Tachyarrhythmias
Atrial Fibrillation
Atrial Flutter
Paroximal atrial tachycardia

Administration
Administer slowly by direct IV injection over
minimum of 5 minutes (longer if given
undiluted)
Do not administer if precipitate present
Drug is severe skin irritant when given IV/IM
and may cause severe local skin reaction with
possible sloughing

Contraindication and Precaution
Hypersensitivity
Uncontrolled Ventricular Arrhythmias
AV block
Constrictive Pericarditis
Idiopathic Hypertrophic Subaortic Stenosis

Use cautiously in
Renal & Hepatic impairment
Electrolyte imbalance
Myocardial Infarction
Thyroid Disoder
Obesity
Elderly Patient
Pregnancy
Breastfeeding infant

Adverse Effects
Dizziness
Mental disturbances
Diarrhea
Headache
Nausea
Vomiting
Maculopapular rash

Extraction and Isolation of Digoxin
1. Initial Extraction & removal of Phenolic compound by precipitation:
i. Extract 20 ml of powdered herb with 100 ml of ethanol 70% by
warming on Hot Plate for 20 min
ii. Cool and filter or centrifuge to remove solid plant residue.
iii. To filtrate add 150 ml water & 20 ml strong solution of Lead
Acetate, the Phenolic compound would ppt as insoluble lead.
09 May 2020 14

iv. Centrifuge the mixture & pipette out & add 10% H2SO4
drop wise until it precipitate forms.
v. This treatment removes excess of lead ions as insoluble
Lead Sulphate
09 May 2020 15

2. Solvent partition to Remove Cardenolides from Aqueous Solution
(i) Centrifuge the mixture & pipette off & extract with 50 ml CHCl3
(ii) Wash with 20 ml water to remove any residual Lead ions
(iii) Separate Chloroform extract & dry using anhydrous sodium
Sulphate & Filter Chloroform into Round bottom Flask

CHEMICAL TESTS
Raymond test:
A small quantity of glycoside is dissolved in 1ml of 50%
ethanol followed by addition of 0.1 ml of 1% solution of
dinitrobenzene in methanol. To this solution 2 – 3 drops
of 20% sodium hydroxide solution is added. Appearance
of violet color changes to blue color.
Legal test :
Glycoside + few drops of pyridine and 1 drop of 2%
sodium nitroprusside and a drop of 20% NaOH is added.
Deep red color occur
Tollens test:
Mixture of pyridine & ammonical silver nitrate gives
silver mirror on wall of test tube.

Continue….
Keller killani test:
Drug + 10ml of 70% alcohol for few minute and filtered.
To 5ml filtrate 10ml of hydrogen peroxide and 0.5 ml of
strong solution of lead acetate is added. To this mixture 1 or
2 drop of concentrated sulphuric acid is added. Appearance
of blue color confirms presence of deoxy sugar.
Baljet test:
Section of digitalis + add sodium picrate solution yellow to
orange color.
Antimony trichloride test:
Solution of glycoside is heated with antimony trichloride
and trichloroacetic acid to obtain blue or violet color.

Continue….
Liebermann test:
Solution of glycoside in chloroform is added in
acetic anhydride followed by conc. sulfuric acid
gives violet to blue color. This test is for
conformation of steroidal nucleus.
Xanthohydral test:
A red color is produced by deoxy sugar when
they are heated with 0.125% solution of
xanthohydral in glacial acetic acid.

Structure Elucidation
Molecular Formula: C41H64O14
Molecular formula:
Molecular Weight: 780.9 g/mol
Physical Description:
Digoxin appears as clear to white crystals or white
crystalline powder. Odorless. Used as a cardiotonic drug.
Taste: Bitter
Melting Point: 249.3°C (480.7 °F)

» Digoxin
1. Sugar:
Digoxin consist of three sugar residue (glycone) and non-
carbohydrate aglycone moeity digoxigenin.
The most commonly found sugar in cardiac glycosides are
D-glucose, D-digitoxose, L-rhamnose & D-Cymarose.
All aglycone represent similar set of Pharmacological
action .
Continue….

Continue….
It is the sugar moeity attached to the aglycone play an
important role in governing Duration of Action, Partition
Coefficient, Absolute Potency and Protein Binding
properties of glycosides.
It is also play an important role in inhibition enzyme
induced metabolic change in the aglycone configuration.
The presence of O-acetyl group on a sugar greatly affects
the lipophillic characters and Pharmacokinetic of the entire
glycosides.

Continue….
2. Aglycone:
Aglycone portion of cardiac glycoside is a steroid nucleus with a unique set
of Fused rings, which makes these agent easily distinguished from the
steroids.
Such ring Fusion gives the aglycone nucleus of Cardiac Glycosides the
characteristic ‘U’ shape.
Hydroxyl group are located at C-3 site of the sugar attached and at C-14
position.
The lactose ring at C-17 is another major stucture feature of cardiac
glycosides
Removal of sugar portion allows epimerization of the 3, 8 –OH group with
decrease activity And increase toxicity due to change in polarity.
The activity of compound depend to a great extent on position of 23rd
Carbonyl oxygen.

Reference
https://www.slideshare.net/AmlendraYadav/digoxin-19788368
https://www.webmd.com/drugs/2/drug-4358/digoxin-
oral/details
https://www.drugs.com/digoxin.html
https://shodhganga.inflibnet.ac.in/bitstream/10603/62880/13/13
_chapter%206.pdf
https://en.wikipedia.org/wiki/Digoxin
https://www.slideshare.net/krishnatummala1/digoxin-and-
gnsenosides
https://www.slideshare.net/NikhilVaishnav3/digitalis-nikku-ppt

Extraction , Isolation and Structure Elucidation of Digoxin

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