Sub: Pharmaceutical Chemistry-II

Topic: Diagnostic agents

Diagnostic agents
Definition: As indicated by the name, Diagnostic agents are used as the
aids in the clinical diagnosis of a disease condition.
These agents are used totally diagnostically.
One essential characteristic of these compounds is that they should not
have any pharmacological action in the body. In fact, any such action is
considered as a side effect.
Classification of Diagnostic agents

1. X-ray contrast media (Radiopaque contrast media)

a. Water soluble eg. Diatriazoic acid, Iodipamide, Iothalamic acid
b. Water insoluble eg. Iopanoic acid, Propyl iodone etc.
2. Drugs used to test organ functions
a. Diagnostic Dyes
i) Used for kidney/renal function test eg. Indigocarmine, Aminohippuric acid, Phenolsulphophthalein
ii) Used for liver function test eg. Sulphobromophthalein
iii) Miscellaneous eg. Evans blue (to determine blood volume), Fluoresceine sodium (to detect corneal
ulcers and presence of foreign bodies in the eye)
b. Other compounds
i) Inulin – To measure G. F. R. (Glomerular Filtration Rate)
ii) Mannitol – For Renal function test
iii) Histamine – To test secretory function of stomach
iv) Pentagastrin – To study gastric function
v) Xylose – To study malabsorption from the G.I. tract
vi) Sodium benzoate – For liver function test (because of its excretion as Hippuric acid)
X-ray contrast media/Radiopaque
substances
The X-ray contrast media are the agents which have the ability to absorb the
x-rays. In other words, these agents can block the passage of x-rays and are
opaque to x-ray examination.
As the x-rays are not able to pass through a radiopaque substance, the
different anatomical organs containing radiopaque substance become visible
on a developed x-ray film.
These agents are used in the examination of G. I. tract, gall bladder, bile duct,
ureter, kidneys, fallopian tube etc.
Most of the radiopaque contrast media are organic iodinated compounds.
However, some inorganic compounds such as Barium Sulphate are also useful.
What are X-rays and how do they work? (This slide is just for understanding how
the x-rays work)
X-rays are a type of radiation that can pass through the body. One can not see the
X-rays by the naked eye and can not feel them too.
As the X-rays pass through the body, energy from the X-rays is absorbed by
different parts of the body at different rates.
A detector placed on the other side of the body picks up the X-rays after they have
passed through, and turns them into an image.
Dense parts of the body that X-rays find it more difficult to pass through, such as
bone, show up as clear white areas on the image. obtained on an X-rays film which
is developed.
On the other hand, softer parts of the body through which X-rays can pass through
more easily, such as lungs, g. i. tract, heart etc. show up as darker areas.
X-rays can be used to examine most areas of the body, mainly used to look at the
bones and joints for fractures etc.
However, X-rays can also be used to detect problems affecting soft tissues, such as
internal organs, but in that case some agent such as Barium meal is required to be
administered.
Iodinated radiopaque compounds:

Iodine is an element which has the ability to absorb the x-rays.

The inorganic iodine compounds are generally toxic, therefore the organic compounds in which
iodine is covalently bonded are used as radiopaques. Compounds such as Iopanoic acid, Propyl
Iodone and others are useful.
Iopanoic acid
Properties:
1. It occurs as a white or cream coloured powder.
2. Practically insoluble in water.
3. Should be protected from light.
Action and Uses:
4. Iopanoic acid is categorised as iodine containing radiopaque contrast media.
5. It is used by mouth for x-ray examination of biliary duct.
Official Preparations:
Iopanoic acid, B. P.
Iopanoic acid Tablets, B. P.
Propyl iodone
It is an iodinated pyridine derivative used as a radiopaque agent.
Chemically it is a propyl ester of an acid Diodone.
Properties:
1. Occurs as a white to almost white crystalline powder.
2. It is practically insoluble in water.
3. Aqueous suspension of Propyl iodone has a Ph of 6-7.5.
4. It is stored at a temperature between 10-30 degrees centigrade.
However, the oily suspension is stored below 30 degrees centigrade.
Action and Uses:
1. Propyl iodone is categorised as an organic iodine containing
radiopaque contrast media.
2. Usually used as a 50% aqueous or 60% oily suspension, prepared
aseptically for the examination of the bronchial tract.
Official Preparations:
Propyl Iodone, B. P.
Propyl Iodone Suspension, B. P.
Propyl Iodone oily Suspension, B. P.
Diagnostic agents for Organ Function Tests:

Chemical compounds belonging to various chemical classes are

employed for testing the functioning of various body organs, such as
kidneys, liver, cardiovascular system, G. I. system and even certain
glands like Hypothalamus, Pituitary gland etc.
Certain dyes are used as Diagnostic agents. Among these, official dyes
are Sulphobromophthalein sodium, Phenol sulphophthalein sodium
and Flurosceine sodium which are all phthalein dyes.
(Note: Phthalein dyes are formed by condensation of phthallic acid with
different phenols)
Sulphobromophthalein sodium
Properties:
1. Occurs as a white crystalline powder.
2. Odourless with a bitter taste.
3. Soluble in water.
4. Hygroscopic in nature.
5. Aqueous solution gives intense purple colour when a few drops of 1 N NaOH are added
to it. The colour disappears on adding an acid.
Action and Uses:
1. Sulphobromo phthalein sodium is categorised as a diagnostic agent.
2. The dye is used for liver function test.
3. It is given intravenously and the amount of dye remaining in blood is estimated after a
specified time interval.
Official Preparations:
Sulphobromophthalein sodium, B. P., I. P.
Sulphobromophthalein sodium Injection, I. P.
Another dye, phenol sulphophthalein is used for renal function test such as
to determine the rate of excretion of the dye in the urine after intravenous
injection. Alkaline urine is coloured red to violet.

Another compound, Inulin which is a polysachharide is given by slow i. v.

injection to measure the G. F. R.
Mannitol which is a hexa hydroxyl alcohol is also used for renal function test.
Histamine, Pentagastrin and Xylose are used for gastric function test.
Histamine is given parenterally as a diagnostic agent to check the secretory
function of the stomach.
Sodium benzoate is used in liver function test and is given by mouth or
intravenously.
Fluorescein sodium
Properties:
1. Fluorescein sodium occurs as a orange coloured dye.
2. Freely soluble in water.
3. Chemically, it is a xanthane derivative.
Action and Uses:
1. Fluorescein sodium is categorised as a diagnostic agent.
2. Commonly used as a sterile 2% w/v solution in ophthalmic practice to detect the corneal lesions, ulcers
and presence of foreign body in the eyes.
3. When instilled into the eye, it does not stain the normal cornea, but lesions or any other part which is
deprived of the epithelium are stained green. Whereas foreign bodies are seen surrounded by a green
coloured ring.
4. Fluorescein sodium is also used in the fitting of hard contact lenses in order to ensure the correct fit.
5. Fluorescein sodium is given by rapid i. v. injection for determination of the circulation time.
6. For visualisation of the gall bladder and the bile duct, it is given intravenously about four hours before
the surgery.
Storage conditions:
Since it is hygroscopic, it should be stored in tightly closed light
resistant containers.

Official Preparations:
Fluorescein sodium, B. P., I. P.
Fluorescein sodium Eye drops, B. P.
Fluorescein sodium Injection, B. P.
Indigocarmine, I. P./Indigotin disulphonate sodium, U. S. P.
Properties:
1. Blue coloured powder or crystals.
2. Sparingly soluble in water.
3. Affected by light.
4. Solutions sterilised by autoclaving or filtration.
Action and Uses:
5. Indigocarmine is categorised as a diagnostic agent.
6. When administered intravenously in the dose of 40 mg, it can be used to test
renal function (by estimating the rate of excretion of the dye in the urine).
7. It can be used to locate the urethral orifice.
8. In the laboratory, it is used as a colouring agent.
Evan’s Blue
Properties:
1. It is a complex azo dye which is used as a diagnostic agent.
2. It occurs as a blue crystalline substance with a greenish lustre or as
a brownish powder.
3. Very soluble in water, slightly soluble in alcohol.
4. Practically insoluble in organic solvents.
5. Aqueous solutions are stable and are sterilised by autoclaving.
Action and Uses:
1. Evan’s Blue is categorised as a diagnostic agent.
2. Used to determine the blood volume.
3. When a 0.45% w/v solution is administered by i. v. injection, the dye
combines with the plasma albumin, giving a specific colour. The
colour produced is directly proportional to the concentration.
Official Preparations:
Evan’s Blue Injection, I. P.
Congo Red
Properties:
1. Occurs as a brownish red powder.
2. Soluble in water and ethanol.
3. Insoluble in ether.
4. Aq. Solutions are sterilised by autoclaving or filtration.
Action and Uses:
5. Congo red is used as a diagnostic agent in amyloidosis.
6. Given by slow i. v. injection and the % decrease in the dye content in the
serum or plasma over a period of one hour is estimated colorimetrically.
7. In normal individuals, 10-30 % of the dye disappears in one hour, while in a
person with amyloid disease, the decrease in the content is about 30-100 %.
Sr. Diagnostic agent Use/Uses
No.
1 Sulphobromophthalein Liver Function Test
2 Fluoresceine Sodim Corneal lesions, Foreign body, For fitting of hard contact lens
3 Indigocarmine/Indigotin Renal Function Test
disulphonate
4 Evans Blue To determine blood volume
5 Congo Red Amyloid disease
6 Iopanoic acid X-ray examination of biliary tract
7 Propyl iodone X-ray examination of bronchial tract
8 Inulin To measure GFR
9 Mannitol Renal Function Test
10 Histamine Gastric Function Test (To check secretory function of stomach)
11 Pentagastrin Gastric Function test
12 Xylose Gastric Function test (To study malabsorption from the G.I. tract)
13 Sodium Benzoate Liver Function test
Questions:
1. Define and classify Diagnostic agents, giving suitable examples.
2. Discuss/Short note: X-ray contrast media (Radiopaque substances).
3. Name the x-ray contrast media you studies and give their uses.
4. Give the properties, uses, official preparations of the following:
Sulphobromophthalein sodium
Evans Blue,
Indigocarmine,
Congo Red
Iopanoic acid, Propyl Iodone
What are X-rays and how do they work?
X-rays are a type of radiation that can pass through the body. One can not see the X-rays by
the naked eye and can not feel them too.
As the X-rays pass through the body, energy from the X-rays is absorbed by different parts
of the body at different rates.
A detector placed on the other side of the body picks up the X-rays after they have passed
through, and turns them into an image.
Dense parts of the body that X-rays find it more difficult to pass through, such as bone,
show up as clear white areas on the image. obtained on an X-rays film which is developed.
On the other hand, softer parts of the body through which X-rays can pass through more
easily, such as lungs, g. i. tract, heart etc. show up as darker areas.
X-rays can be used to examine most areas of the body, mainly used to look at the bones
and joints for fractures etc.
However, X-rays can also be used to detect problems affecting soft tissues, such as internal
organs, but in that case some agent such as Barium meal is required to be administered.