Qc of radiopharmaceuticals

Quality control and applications of
Radiopharmaceuticals

Presented by
Presented by
Savita patil
Savita patil
M.Pharm IIIrd sem
M.Pharm IIIrd sem
(Pharmaceutics)
(Pharmaceutics)
Govt. college of pharmacy,
Govt. college of pharmacy,
Powerpoint Templates Aurangabad.
Aurangabad.
Page 1

Snapshot
Snapshot

Introduction

QC of radiopharmaceuticals

Applications

References

Powerpoint Templates
Page 2

Introduction

Radiopharmaceuticals are unique medicinal formulations
containing radioisotopes which are used in major clinical areas for
diagnosis and/or therapy.
A radiopharmaceutical contains a radioactive moiety with a
biodistribution moiety.
After administration radiophamaceutical localizes in a specific
organ/ tissue depending on biodistributing moiety.

Page 3

QC tests of
QC tests of
radiopharmaceuticals
radiopharmaceuticals

QC of radiopharmaceuticals includes:
The purity
Potency
Biologic safety
Sterility and
Efficacy of the radiopharmaceuticals.
The tests should be faster and effective since
radionuclide
have short half life.
Page 4

The QC tests for most of the radiopharmaceuticals are

mentioned in pharmacopoeia (EP, BP, etc)

The quality control system should include a procedure which

describes measures to be taken if unsatisfactory test results are

obtained.

Page 5

Different quality tests
Different quality tests

Page 6

Parameters of each test
Parameters of each test

Page 7

A. Physical tests
A. Physical tests

1.pH and ionic strength:
 Ideally pH should be 7.4, but it can vary from 2-9.
 Correct ionic strength achieved by addition of an acid or
alkali.
2. Physical characteristics:
 Recognize the color and state of a radiopharmaceuticals
 Colloidal or aggregated preparations : Identify size by
microscope with haemocytometer.
Page 8

Importance of particle size determination
Importance of particle size determination

Size of particles will determine the site where the

radiopharmaceutical will get localized.

E.g. 99mTc MAA, Tc-labeled albumin microspheres : 10

to 100 µm

If>100µm: cause pulmonary embolism

If <10 µm: Deposits in the reticuloendothelial cells.
Page 9

B. Radiochemical tests
B. Radiochemical tests

1. Radionuclidic Purity:
 % of the total radioactivity that is present in the
form of the stated specified radionuclide
 Determined by measuring the half-lives and
characteristic radiations emitted by individual
radionuclides.
 γ-ray emission radionuclides : checked with
multi-channel analyzer
 Pure β emission radionuclides : checked with β-
spectrometer or a liquid scintillation counter

Page 10

2. Radiochemical purity:

It is the proportion of the radionuclide present in the stated chemical form.

Radiochemical purity can be determined any separation technique, and

measurement of radioactivity.
% RCP= radioactivity in the desired chemical/ radioactivity of total

radiopharmaceutical x 100
Radiochemical impurities may arise from decomposition due to:
(1) action of solvent
(2) change in temperature or pH
(3) light
(4) presence of oxidizing or reducing agents
(5) radiolysis

Page 11

Page 12

TLC of radiopharmaceuticals

Radiopharmaceutical Stationary phase Mobile phase

14
C-urea cellulose butanol-water-acetic acid (12:5:3)

123/131
I-hippuran Silica gel chloroform-acetic acid (9:1)

131
I-iodocholesterol Silica gel chloroform-ethanol (1:1)

111
In-octreotide Silica gel 0.1 M citrate buffer pH 5

123
I-iomazenil Silica gel ethyl acetate-ammonia
(200:1)
Page 13

Radioactivity

Necessary to determine since radioactivity will determine the radiation
dose to each patient.
It is expressed in SI unit Bequrrels (Bq) or Curie, a non SI unit.
Where 1 Bq=1 disintegration/sec
Activity determinations are carried out by isotope dose calibrator.
Calibration of dose calibrator Should be done by a reference source,
e.g. Co 57,Ra-226 or Cs-137

Page 14

Radioactivity Testing

Page 15

1. Geiger Muller counter

Principle: Property to cause ionization of a gas,e.g. Argon.
Beta particles enter the G-M tube through Mica window

Argon gas is ionized

Argon ions are attracted to negative electrode.

Process continues and net result is to ionize whole vol. of tube equivalent to
current

Amplification Digital/ audio output

Page 16

Geiger Muller counter

Page 17

Conti……………….

Advantage:

It provides a high output

Disadvantage:

Efficiencies are low for low energy Beta emitters e.g. 3H.

Page 18

2. Liquid scintillation counter

Principle: Property of radiation to cause fluorescence.

Advantage: can be used for low energy beta emitters, e.g. 3H and 14C.

Problem :

1. sample preparation: Requirement to have a clear solution or

dispersion in non aqueous solvent.

2. variable quenching: may reduce efficiency.

Page 19

Method

Sample is dissolved in solvent with a scintillant material, e.g. Diphenyloxazole

Ionizing radiation(B particles) transfers energy from solvent to scintillant
molecule

Molecules are excited to higher state and latter on fluoresce with emission of
light

Detected by photomultiplier

Page 20

Liquid Scintillaton Counter

Page 21

Isotope dilution analysis:

• General two methods:

• 1.Direct method: Determination of an inactive compound by
dilution with a radioactive compound.
• 2.Reverse method: Involves the estimation of radionuclide by
dilution with an inactive nuclide

Page 22

C. Biological tests

1. Sterility:
1. Sterility:
 Sterility: It is complete absence of live micro organisms and its spores.
Sterility: It is complete absence of live micro organisms and its spores.
 Methods used:
Methods used:

 Procedure: incubate radiopharmaceutical with growth medium
 Procedure: incubate radiopharmaceutical with growth medium
containing 14C glucose.
containing 14C glucose.

Bacteria (if any) will metabolize glucose releasing 14CO2.2.
Bacteria (if any) will metabolize glucose releasing 14CO

Detection of amounts of radioactivity greater than background indicates
Detection of amounts of radioactivity greater than background indicates
bacterial growth.
bacterial growth.

Page 23

Cont…

2. Incubate the radiopharmaceutical sample in fluid thioglycolate
2. Incubate the radiopharmaceutical sample in fluid thioglycolate

medium at 30to 35ºC for 7 to 14 days For detection of anaerobic bacteria,
medium at 30to 35ºC for 7 to 14 days For detection of anaerobic bacteria,

or
or

3. Soyabean-casein digest medium for incubation at20 to 25ºC for 7 to 14
3. Soyabean-casein digest medium for incubation at20 to 25ºC for 7 to 14

days. For detection of fungi and aerobic bacteria.
days. For detection of fungi and aerobic bacteria.

And growth of micro organisms is seen.
And growth of micro organisms is seen.

Page 24

2. Pyrogen testing

LAL(Limulus ambeocyte lysate) test can be used.
LAL (Limulus ambeocyte lysate) test can be used.

Methodinvolves incubation of product with lysate of circulating ambeocytes
Method involves incubation of product with lysate of circulating ambeocytes

of aahorseshoe crab (Limulus polyphenus) . .
of horseshoe crab (Limulus polyphenus)

Presence of pyrogens will cause the lysate to form the gel.
Presence of pyrogens will cause the lysate to form the gel.

Page 25

3. Biodistribution

Importantto determine that the agent does localize in the organ of
Important to determine that the agent does localize in the organ of
interest.
interest.
Procedure:
Procedure:
Administration of radiopharmaceutical in animals
Administration of radiopharmaceutical in animals

Ascertain the relative quantity of radioactivity in various organs.
Ascertain the relative quantity of radioactivity in various organs.

Page 26

Other QC tests

Apart from above mentioned tests the final product container should be
checked for proper labeling prior to release of product.
Written procedure should be for dealing with products failing to meet the
required standard.
 investigation measures taken to prevent future events
documented.
Release can only be effected if:
The product complies with the specifications
 The product has been prepared according to Good Radiopharmacy Practice

Page 27

Labelling :

• the name of the product and the name of the radionuclide;
• any product identification code;
• the name of the manufacturer;
• an identification number (batch number);
The label on the • for liquid preparations, the total radioactivity in the container, or the
outer package radioactive
• concentration per millilitre, at a stated date and, if necessary, hour,
should include : and the volume of liquid in container;
• for solid preparations, such as freeze-dried preparations, the total
radioactivity at a
• stated date and, if necessary, hour;
• for capsules, the radioactivity of each capsule at a stated date and, if
necessary, hour and the number of capsules in the container;
• where relevant, the international symbol for radioactivity.

Page 28

Applications of Radiopharmaceuticals

Page 29

Page 30

Therapeutic Applicatios
Of
Radiopharmaceuticals

Radiolabelled Molecules Disease

Chromic Phosphate P32 For Lung, Ovarian, Uterine, And
Prostate Cancers

Sodium Iodide I 131 Thyroid Cancer

Samarium Sm 153 Cancerous Bone Tissue

Sodium Phosphate P 32 Cancerous Bone Tissue And Other
Types Of Cancers

Strontium Chloride Sr 89 Cancerous Bone Tissue

Page 31

References

1. www.scribd.com

2. Beckett A.H., Stenlake J.B.; “Practical pharmaceutical chemistry”;4 th

edition; CBS publication; pg. no. 509-511.

3. IP 2007; vol 1.;2.2.12; , pg.no. 53-54.

4. “The radiopharmacy-A technologist’s guide”; pg.no.22

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Qc of radiopharmaceuticals

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