Potentiometri

c Titration
By Ali Abbas
Potentiometry
 Potentiometry is an electroanalytical
method which is based on measurement
of potential of an electrode system under
the conditions of no current flow.
Potentiometric measurements enable
selective detection of ions in presence of
other substances.
Electrochemical Cell
 The electrochemical cell is a device in which a
redox reaction takes place indirectly and the
decrease in potential energy of the reaction
appears largely in the form of electrical energy.
 Electric current results from a chemical reaction; in
which oxidation (loss of electrons) occurs at one
electrode and reduction (gain of electron) at the
other electrode. Oxidation and reduction occur
simultaneously. Oxidation occurs only if reduction
take place at the same time. This can be
illustrated by taking a few examples.
 1 . Zn-CuSO4 reaction in a beaker (oxidation
of zinc metal by Cu++ ions).
 If a zinc rod is placed in a solution of
copper sulphate, the following observation
will be made. The zinc strip starts dissolving
forming Zn2+ ion in a solution (oxidation):
 Zn (s) → Zn2+(aq) + e_
 At the same time, copper starts precipitation
out from the solution is due to reduction of
Cu2+ present in a solution of copper metal:
 Cu2+(aq) + 2e_ → Cu(s)
 Both reactions are called half reactions where the
first reaction and second reaction are referred as
oxidation half reaction and reduction half
reaction respectively. The overall redox reaction is
obtained by summation of two half reactions:
 Zn(s) + Cu2+ (aq) → Zn2+ (aq) + Cu (s)
 The reaction is exothermic i.e. accompanied by
evolution of heat. Hence ΔH is negative. The
decrease of potential energy appears as heat.
 Possibility of reverse reaction is nil (copper rod in a
solution of zinc sulphate); it means, zinc metal can
be oxidized by Cu2+ ion but Copper metal cannot
be oxidized by Zn2+ ions.
2 . Cu-AgNO3 reaction in a beaker
(oxidation of copper metal by Ag++ions).
 Cu(s) + 2Ag+ (aq) → Cu2+(aq) + 2 Ag(s)
 Copper can be oxidized by Ag+ ion but
silver cannot be oxidized by copper.
Redox Reaction in
Electrochemical Cells
 Due to the redox reaction in
electrochemical cells, the decrease of
potential energy appear as electrical
energy. It can be explained by the
following experiment.
Procedure
 Take a dilute (0.1 ml) solution of copper
sulphate in one beaker and a dilute solution
of zinc sulphate in an another beaker. Put a
copper rod in the copper sulphate solution
and zinc rod in the zinc sulphate solution.
 Connect one end of metal rod (zinc rod)
to one terminal of ammeter and other
(copper rod) through variable resistance to
the other terminal of the same ammeter.
Finally connect the two solutions with each
other through a glass tube containing a
solution of potassium sulphate (salt bridge).
 Ifthe metal rods are not connected to
each other or if salt bridge is taken out, no
current flows through the ammeter and
no reaction takes place in the cell. But, as
soon as the connection is made, the
current starts flowing as indicated by the
reading.
 Zn(s) + Cu2+(aq) → Zn2+(aq) + Cu(s)
 The current continuous to flow as long as
chemical reaction continues to take place. If
the flow of current is stopped after some time
by disconnecting the wire and metal rods are
washed, dried and weighed. It will be seen
that zinc rod has lost in mass, while copper
rod has gained in mass. The gain and loss in
mass in copper and zinc rod take place
according to faraday’s second law.
Loss in mass of zinc rod/gain in
mass of copper rod
 The loss in mass of zinc rod is due to passing of zinc metal
into solution as Zn2+ ions:
 Zn(s) -------- Zn2+(aq) + 2e_
 This is an oxidation half reaction. The electrons thus
released accumulate in the zinc rod, move into ammeter
and then through the resistance, enter the copper rod
there, then taken up the Cu2+ ions which are discharged as
copper metal (s) on the copper electrode.
 Cu2+(aq) + 2e_ ----------- Cu(s)
 This is reduction half reaction thus the number of electrons
liberated in one half reaction is equal to number of
electron consumed in another half reaction.
 Itis also observed that no heat is evolved
in present case, whereas a large amount
of heat (about 212 KJ per ‘g’ of zinc
changing into Zn2+ ions) is evolved when
the same reactions take place in a
beaker.
The Daniel cell
 The galvanic cell in which the Zn-CuSO4
reaction takes place is called Daniel cell.
It differs from the electrochemical cell.
There is no salt bridge in the present case.
Zinc sulphate is placed in a porous pot
while copper sulphate is placed in a glass
vessel. The two solutions can seep through
the porous pot with each other
automatically.
Relative tendencies of electrodes to liberate
electrons
 When two electrodes are joined to form a cell, a
competition sets in between two electrodes to
liberate electrons. In the cell of Zn-Cu electrodes,
zinc has greater tendency to liberate electrons
than copper. The electrons flows from zinc to
copper. Zinc, therefore acts as the negative
electrode white copper acts as the positive
electrode. In the cell of Cu-Ag electrodes copper
electrodes has greater tendency to liberate
electron.
 In Zn-H2 cell, zinc has greater tendency to
liberate electrons. So it acts as negative
electrode while hydrogen (gas) electrode act
as a positive electrode. If, however, a Cu-H2
(g) cell is set up, hydrogen (gas) having
greater tendency to liberate electrons then
hydrogen act as negative electrode while
copper act as the positive electrode. From
these observations, various electrodes can be
arranged in decreasing order of tendencies
to liberate electrons.
 Zn > H2 > Cu > Ag
 According to convention, the electrode at
which electrons are released is written to the
left while at which electrons are taken up is
written on the right while keeping this view,
the Zn-Cu cell (Daniel cell) can be written as:
 Zn/ZnSO4 || CuSO4/Cu
 A single vertical line represents a phase
boundary across which a potential difference
exists. The double vertical line signifies a
boundary between two solutions of different
composition across which a potential
difference exists.
Theory
 The main theory involved in the potentiometry is, when the
known potential electrode immersed in the sample solution
then the potential is given by Nernst equation:
 E= E0 +(0.592/n) log c
 Where E is the potential of the solution;
 E0 is the standard electrode potential
 n is the valency of the ions
 c is the concentration of the sample solution
 0.592 is the value obtained from the RT/F
 where R is the gas constant
 T is the temperature in Kelvin
 F is the faradays constant.
Principle
 The principle involved in the
Potentiometry is when the pair of
electrodes is placed in the sample
solution it shows the potential difference
by the addition of the titrant or by the
change in the concentration of the ions.
Instrumentation
Electrodes
 These are mainly used to measure the
voltages. Mainly two electrodes are used
in the potentiometry .They are as follows

 Reference electrode
 Indicator electrode
Reference electrode
 The reference electrode is the electrode which
contains of its own potential value and it is stable
when dipped into sample solution. The salt bridge
is used to prevent the interference of the analyte
solution with that of reference solution. Here
analyte solution is the solution whose potential is to
be measured.
 These are mainly used for the determination of the
analyte by maintaining the fixed potential.
 Standard hydrogen electrode
 Silver-silver chloride electrode
 Saturated calomel electrode
 The reference electrodes are classified
into two main classes they are as follows
Primary standard electrodes
 Standard hydrogen electrode
Secondary standard electrodes
 Silver-silver chloride electrode
 Saturated calomel electrode
Indicator electrode
 The indicator electrode is the electrode which
responds to change in the potential of analyte
solution. The electromotive force of the complete
cell is given by the following equation:
 Ecell = Ereference + Eindicator + Ejunction
 where
 Ereference is the electromotive force of the reference
electrode,
 Eindicator is electromotive force of indicator
electrode,
 Ejunction is the electromotive force at the junction of
the liquid.
 Indicator electrode is used to measure the
potential of the analyte solution comparing with
that of reference electrode. Its potential is directly
proportional to ion concentration.
Example
 Hydrogen electrode.
 Glass electrode.
 Antimony –antimony oxide electrode.
There are two classes of indicator electrodes:
 Metal indicator electrodes
 Ion-selective electrodes
Metal indicator electrodes
 These develop electric potential in
response to redox reaction on the metal
surface.
 Platinum or Au are used as metal
indicator electrodes.
 These are mainly classified into three types
of electrodes used in the potentiometry.
They are as follows.
First kind electrodes
 They are composed of the metal rod
immersed in its metal solution. These
electrodes respond to the ionic activity of
the electrode.
Example
 Silver electrode dipped in the silver nitrate
solution.
 Copper electrode dipped in the copper
sulphate solution.
Second kind electrodes
 These are composed of the metal wires coated with
the salt precipitates. These electrodes respond to the
changes in the ionic activity through the formation of
the complex.
Example
 Ag/ AgCl/ KCl Hg/ Hg2Cl2/ KCl
Third kind electrodes
 These electrodes are also known as inert electrodes
and redox electrodes. They are composed of inert
metal electrode immersed in the redox solution.
Example
 Pt-H2 electrode
Ion selective indicators
 These are composed of ion-selective
membrane by which the ion crosses and it
creates the imbalance.
Example
 Glass membrane electrode
 Antimony – antimony oxide electrode.
 Glass electrode
E.M.F. of cell and its measurement
 The flow of electricity from one electrode
to other electrode in a galvanic cell
indicates that two electrodes have
different potential. The difference of
potential which causes flow of current
from one electrode (at higher potential)
to another electrode (at lower potential)
is called the electromotive force (E.M.F).
 The (E.M.F.) of cell can be measured by
connecting the two electrodes to the two
terminals of voltmeter. The potential difference is
then read directly from the instrument. This
method, however, suffers from two defects. Firstly,
as some current is drawn from the cell during the
process of measurement, chemical reaction
occurs to some extent. Secondly, with flow of
current, a part of the E.M.F. is used up in
overcoming the internal resistance of the cell.
Hence, the potential difference, as read from the
voltmeter, will not be correct E.M.F. of the cell.
 E.M.F. of a cell can be measured
accurately only by a method which
involves little or no flow of electricity. Such
a method is based on Poggendorff’s
compensation principle. In this method,
the E.M.F. of another cell or battery is
measured until two E.M.F‘s become equal
and there is no net flow of current in the
circuit. The electrical assembly used is
known as potentiometer.
Potentiometer
 A potentiometer in simple form consists of two
electrical circuits in combination. The first circuit
consists of uniform wire AB of higher resistance. A
storage battery (B) of constant E.M.F. which should
be larger than E.M.F. of the cell to be measured, is
connected at the ends A and B of the wire. The
second circuit is made up of two cell’s X and S
(one of accurately known potential, the other
whose potential is to be determined), a switch, K
to include one or other of the cells in the circuit, a
galvanometer to show the flow of current, and a
sliding contact, D on the length of resistance wire.
 When switch K is closed, the battery, B sends
electricity flowing from the battery B to the end A
of the resistance wire AB. At point A, the current
from battery can divide part of it flowing through
the resistance wire AB and then back to battery B;
the remainder tends to flow through the second
part of the circuit. The tendency for electricity from
battery B to flow in the second circuit is opposed
by the tendency for electricity to form cells Ex and
Es. The galvanometer G then will indicate whether
current is flowing in the second part of the circuit
and in which direction.
 The sliding contact is moved along the wire
AB till no current flows through the
galvanometer. First of all, the Es (of unknown
E.M.F.) is included through switch, S1 and the
sliding contact is moved till no current flows in
galvanometer. Then E.M.F. of the cell, say Ex is
proportional to the distance AD. Then E.M.F.
of the cell, say Es is proportional to the
distance AD1. Then emf of a cell can be
measured.
Types of Potentiometric
titrations
Acid-base titration
Reference electrode
 Saturated Calomel Electrode (SCE)
Indicator electrode
 Quinhydrone, Glass electrode
Redox titration
Reference electrode
 Saturated Calomel Electrode
Indicator electrode
 Platinum Electrode
Complexometric titration
Reference electrode
 Saturated Calomel Electrode
Indicator electrode
 Silver Electrode or mercury Electrode
Precipitation titration
Reference electrode
 Saturated Calomel Electrode
Indicator electrode
 Silver-Silver Chloride Electrode
Diazotization titration
Reference electrode
 Saturated Calomel Electrode
Indicator electrode
 Glass Electrode
APPLICATIONS
Clinical chemistry
 Ion selective electrodes are present sensors for clinical
samples because of their selectivity for analyte in complex
matrices. The most common analytes are electrolytes such
as Na, k, Ca, H, and Cl and dissolved gases such as CO2
Environmental chemistry
 For analysis of CN- ,NH3, NO3, in water and waste water.
Potentiometric titrations
 For determining the equivalence point of an acid base
titration possible for redox, precipitation, acid-base,
complexation as well as for all titrations in aqueous and non
aqueous solvents.
APPLICATIONS
Agriculture
 NO3, NH4, I, Ca, K, CN, Cl in soils, plant materials, feed stuffs,
fertilizers.
Detergent manufacturing
 Ca, Ba, F for studying effects in water quality.
Food processing
 Salt content of meat fish dairy products
 Fruit juices brewing solutions
 Ca in dairy products and beer
 K in fruit juice and wine making
 Corrosive effects of NO3 in canned foods
 F in drinking water and other drinks
 NO3 and NO2 in meat preservatives
Polarography
By Ali Abbas
Introduction
 It is an electroanalytical method of analysis
where time dependent potential is applied to
an electrochemical cell and the current
flowing through the cell is measured as a
function of total potential.
History
 The earliest voltammetric method,
polarographic method of analysis was first
developed by Jaroslav Heyrovsky in 1922, for
that, he received Nobel Prize in 1952 for
developing this technique using dropping
mercury electrode as the working electrode.
Potentiometry vs Polarography
 In potentiometry, zero current is
maintained. But in polarography, limited
current is produced by limited electrolysis.
Hence, it is based on the measurement of
current resulting from reduction or
oxidation of an electro active species, at
a given electrode potential under
controlled condition.
Electrodes
 Asin potentiometry, there is a reference
electrode, saturated calomel electrode
(SCE) and an indicator electrode or
microelectrode in this technique.
Indicator Electrode
 Themicroelectrode or indicator electrode
assumes the potential impressed upon in.
The indicator electrodes may be made
from quite a large number of materials.
Example
 For instance, mercury, platinum, gold and
graphite, having varying shapes and
construction can be used.
 Mostly, DME (Dropping mercury electrode) is
used as indicator electrode. The apparatus is
designed in such a manner that electrolysis of
electroactive species take place at the
indicator electrode and the potential of
micro electrode is always measured relative
to reference electrode.
Reference Electrode
 The SCE consists of large surface area so
that current density (current per unit area)
is small at this electrode. Its potential will
then essentially constant and unaffected
by applied potential (emf).
Definition
 The electrode potential of growing
mercury electrode in electrolyte
containing electroactive species is varied
as a function of time and resulting current
is measured.
Theoretical Concept
 The principle of polarography can be
explained with help of simplified
polarographic apparatus which contain a
reducible species (RS) such as nitrofurantoin
and supporting electrolyte (KCI) in a
electrolysis cell. When the movable contact
‘m’ is placed at the extreme left position (say
zero), the potential in the voltmeter ‘V’ will be
zero and the current measured in microamp
(m amp) on the ammeter ‘A’ will also register
zero.
Diagram
Theoretical Concept
 If the contact ‘m’ is now moved to the
light, say to 0.5, a certain voltage will be
impressed across the electrode (readable
in Voltmeter V). Since the microelectrode
is negative, ions (impurities in the salt and
H2O) capable of picking up electrons at
this low potential and will be reduced and
the current flowing through the cell will be
registered.
Theoretical Concept
 Ifthe movable contact is advanced to 1,
a greater voltage will be impressed it
across the electrode (more ions will be
reduced) and increase in current flowing
through the cell will be observed. If we
continue moving the contact, we will
eventually reach a potential, which will
reduce electroactive species.
Theoretical Concept
This effect will be reflected in a relatively
large increase in the current flowing through
the cell on increasing the voltage shows an
increase in the current flowing through the
cell because a greater number of reducible
species RS (nitro-furantoin) are reduced in
the vicinity of electrode. As there is
decrease in the concentration of ion in the
vicinity of microelectrode, the potential of
this electrode will decrease. This is called
concentration polarization.
Theoretical Concept
 However, increasing the potential does
not bring about an increase in the
current. In other words, the current, which
is measured in this region, is diffusion
controlled and depends on the rates at
which the reducible species
(nitrofurantion) Move (diffuse) from the
bulk of solution to the surface of
electrode. The diffusion controlled current
(diffusion current of limiting current) is a
function of concentration.
Instrumentation
Cathode
 It is a dropping mercury electrode.
 It carries negative charge.
 The diameter of capillary tube is 20-50 µm.
 The droplet time is 2-12 seconds so 5-30
drops per minute can be produced.
 Applied voltage range is + 0.4 to – 1.8 V.
Instrumentation
Advantages of DME
 The surface area is always renewable and
eliminate toxic effects.
 The surface is smooth.
Disadvantages of DME
 Capillary can be blocked easily
 Potential range is only + 0.4 to – 1.8 V.
Instrumentation
Anode
 Mercury pool act as a anode.
 It has high surface area.
 No change in potential occur.
 It is a non-polarizable electrode.
 It carries positive charge.
Instrumentation
Solution
 Solution contains electroactive species and
supporting electrolyte.
Electroactive species
 The species which are under investigation are
electroactive species. For instance Pb+2.

Supporting electrolyte
 As we want ions should be transferred by
diffusion only, we have to avoid the transfer of
ion (migration) due to potential gradient.
Instrumentation
Supporting electrolyte (Continued)
 A potential gradient exists between the
electrodes with the microelectrode (usually,
dropping mercury electrod, DME) negative
relative to reference electrode (usually
saturated calomel electrode, SCE). Cations
will move towards the DME under the
influence of this potential and their reduction
give rise to the migration current
(undesirable). Therefore, to reduce the
current carried by the reducible ion, a large
concentration of non-reducible electrolyte is
added to the solution.
Instrumentation
Supporting electrolyte (Continued)
 This substance, the indifferent electrolyte
(or supporting electrolyte) then carries
essentially all of the current and migration
current is eliminated. Commonly used
supporting electrolytes are potassium or
sodium salts. The potassium ions cannot
be discharged at cathode until the
impressed voltage becomes large.
Instrumentation
Supporting electrolyte (Continued)
 The large number of potassium ions therefore
remains as a crowd around cathode and
restrict the potential gradient to a region so
very close to the electrode surface. So there is
no longer an electrostatic attraction
operative to attract other reducible ions from
the bulk of the solution. Under these
circumstances the limiting current is solely
controlled by the diffusion of the
electroactive speies through the
concentration gradient adjacent to the
electrode.
Diagram
Polarogram
 The data in polarography are best
expressed graphically in which current
flow (in amperes) versus potential
variation is plotted along the ordinate. This
graph is called polarogram. A
polarogram has the S shape. The
polarogram is conveniently divided into
three regions as A, B and C.
Diagram
Polarogram
Residual current
 Region A results from the charging current of
the electrode and reduction of traces of
impurities present in the solution. This current is
referred to as residual current. It include
 Faradic current, the current due to impurities
 Non-faradic current or capacitive current, the
current due to electrical double layer
(Helmholtz double layer)
 ir = if + ic
 ir = Residual current
 if = Faradic current
 ic = Capacitive current
Polarogram
Migration current
 This current is due to migration of ions.
 By increasing the concentration of
supporting electrolyte, we can reduce
the migration current.
Polarogram
Diffusion current
 Region B results from the reduction of the
electro active species in solution. The
shape of the curve in the region indicates
that there are more reducible species in
the vicinity of electrode that can be
reduced.
Polarogram
 As the potential of the electrode is increased,
more and more of the reducible species are
reduced (indicated by the sharp rise in the
current) until that point in the curve is
reached where an increase in the potential
does not give an increase in the current. This
indicates that the area in the vicinity of
electrode is depleted of reducible species
and the reduction is then controlled by the
rate at which the species diffuse into this
area. It is directly proportional to the
concentration of electro active species.
Polarogram
Limiting current
 Beyond the certain potential, the current
the steady value called as the limiting
current.
Half wave potential, E1/2
 The electro-active material in polarography is
characterized by its half-wave potential, E1/2.Under
any defined set of experimental conditions, each
substance has its own characteristic E1/2 and this is
the basis of qualitative polarographic analysis. The
half-wave potential is defined as the potential at
which the current due to the reduction or
oxidation of the substance responsible for the
wave is half as large as on the plateau. The half-
wave potential is also independent of the
electrode characteristics and concentration of
the electroactive substance, therefore serves for
the qualitative identification of an unknown
substance.
IIkovic equation
In the presence of excess supporting electrolyte, the
electrical force on the reducible/oxidizable ions is
nullified and therefore, the limiting current is solely a
diffusion current. Ilkovic (1934) examined the various
factors which govern the diffusion current and
deduced a theoretical equation as:
iD = 607 n cD1/2 m2/3 t1/6
 Where
 id = average diffusion current in microamperes
during the life of the drop
 n = the number of electrons consumed in the
reduction or oxidation of one mole of the
electroactive species
 D = diffusion coefficient of the reducible or
oxidizable substance expressed as cm2/second
IIkovic equation
 c = concentration of electroactive species in
millimoles per dm3
 m = the rate of flow of mercury from the dropping
mercury electrode expressed in mg/second
 t = drop time of mercury in seconds
 The constant 607 is a combination of natural
constants, including the Faraday. This is an
important equation because it accounts for the
linear dependence of id upon c keeping all other
factors constant. It is useful in quantitative
polarographic analysis.
Polarographic maxima:
Maxima suppressors
 Current-voltage curves obtained with electro-
reducible ions at DME are frequently distorted
by increasing the current beyond the diffusion
current value and rapidly decrease to the
normal diffusion plateau after a critical value
is reached as the applied potential is
increased. This abnormal increase in current is
referred as maxima which vary in shape from
sharp peaks to rounded humps.
Polarographic maxima:
Maxima suppressors
 To measure the true diffusion currents, the
maximum must be eliminated. This can be
done by adding small amount of surface-
active agents such as gelatin, dye stuff,
Triton X-100 etc. which are likely to form
an adsorbed layer on the mercury-
solution interface to prevent streaming
movement of the diffusion layer at the
interface.
Polarographic maxima:
Maxima suppressors
 Gelatin is widely used in the
concentration range of 0.002 to 0.01%.
Higher concentration will suppress the
diffusion currents also. Others frequently
used are, Trition X-100 (a non-ionic
detergent) in the range of 0.002 to 0.004%
and methyl cellulose (0.005%).
Applications of Polarography
 Polarography is used predominantly for
trace metal analysis of alloys, ulta-pure
metals, minerals/metallurgy,
environmental analysis (air, water, soil and
sea water contaminations), food stuffs,
beverages and body-fluids, toxicology
and clinical analysis.
Applications of Polarography
 Itis also useful in the analysis of vitamins,
alkaloids, hormones, terpenoid
substances and natural coloring
substances, analysis of drugs and
pharmaceutical preparations,
determination of pesticide or herbicide
residues in the foods, in the structure
determination of many organic
compounds etc.
Applications of Polarography
 Thistechnique is used in organic chemistry
for qualitative and quantitative analysis
and structure determinations. Most of the
organic compounds are insoluble in pure
aqueous medium and also in mercury
amalgam. Therefore, the solvent in which
the organic compounds and its electrode
product is soluble is added to the
supporting electrolyte.
Applications of Polarography
 These solvents include various alcohols
and ketones, dimethyl formamide,
acetonitrile, ethylene diamine and others.
The commonly used supporting
electrolytes which are easily mixed with
organic solvents are various quaternary
ammonium salts such as tetrabutyl
ammonium iodide.
Thank You
Q&A
RADIOANALYTI
CAL
TECHNIQUES
ALI ABBAS
M.Phil PharmaceuticAL
CHEMISTRY
Introduction
 The phenomenon of radioactivity was discovered by a
French Physicist Henary Becqueral in 1896. He
observed that a photographic plate wrapped in a
black paper placed near the uranium salt had
become affected. It indicate that uranium salt
emitted certain rays which had penetrating properties.
Becquerel called these rays as radioactive rays and
the property itself called radioactivity. In other words
“The phenomenon of emission of active radiations
from certain substance is called radioactivity and the
substance which emit such radiation are called
radioactive substances”.
Types of Radiochemical
Methods
 Radiochemical methods are characterized by
good accuracy and their ability to adapt to a
wide number of applications. Another
advantage to this method is that they minimize or
even eliminate the need for separations that are
required in other analytical methods.
Radiochemical methods are divided into three
types:
 (A) Activation analysis: Activity is induced in one
or more elements of the sample by radiation or
with suitable particles. Most commonly, thermal
neutrons from a nuclear reactor source is used.
Types of Radiochemical
Methods
 (B) In the second method, the radioactivity is physically
introduced into the sample by adding a measured amount
of radioactive species, called a tracer. The most important
class of quantitative methods is based upon this procedure
(Isotope dilution method) in which a weighed quantity of
radioactivity tagged analyte is added to the sample. After
through mixing to assure homogenicity, a fraction of the
component of interest is isolated and purified. The analysis
is then based upon the determination of this isolated
fraction.
 (C) The third class of method involves the measurement of
naturally occurring radioactivity present in the sample. For
example, measurement of radon in household air and
uranium in pottery and ceramic materials.
Aspects of Nuclear Physics
Atomic Structure
 The atom consist of small heavy nucleus (containing most of the
mass), surrounded by planetary electrons. The nucleus consist of
two fundamental particles (1) Proton – carry a singly positive
charge, (2) Neutron-uncharged.
Atomic number
 It is the number of protons in the nucleus of an atom. It always
remain constant for particular element e.g. C-6, P-15, Na-11
(represented as 6C, 15P, 11Na respectively). It is represented by Z
which is based on the German word zahl meaning number.
Mass number
 It is the number of protons and neutrons present in the nucleus. The
atoms of particular element can have different mass number
because the number of neutrons may vary. Mass number is
represented by A which is based on the German word
atomgewicht meaning atomic weight.
Aspects of Nuclear Physics
Nuclide
 A nuclide is a particular nucleus species
characterized by its atomic number and mass
number. For example, 6C12 and 11Na22 are the
nuclides.
Isotopes
 These are nucleus with the same atomic number
but different mass numbers. E.g. 1H1, 1H2, 1H3 are
isotopes of hydrogen. Isotopes may be stable or
unstable. The unstable isotope shows radioactivity
(Radioactive decay) and so called radioactive
isotopes or radio-nuclide.
Stable and unstable Nuclei
 The nuclei of elements of low atomic
number are most stable if the number of
neutron is equal to or slightly greater (1
more) than number of protons. If the
neutron number is less or slightly greater (2
Protons Neutrons

6 4 Unstable

or more) than number of protons, the

6 5 Unstable

nucleus is unstable e.g. carbon.

6 6 Stable

6 7 Stable

6 8 Unstable
Stable and unstable Nuclei
 For element of higher atomic number, the
most stable neutron: proton ratio
approximates to 1.5:1.
 The unstable (Radioactive) isotopes undergo
spontaneous disintegration to form the stable
isotopes. The disintegration or radioactive
decay of isotopes occurs with the emission of
X-rays or gamma rays; with the formation of
elementary particles such as electrons,
positrons and helium nucleus or by fission in
which a nucleus breaks up into smaller nuclei.
Type of Radiation
Alpha particles
These have the following characteristics:
 They are equivalent to the nuclei of helium atoms,
2He .
4

 They are heavy and positively charged. Its

relatively large mass and charge render alpha
particles highly effective in producing ions pairs
within the matter through which they pass.
 They have low penetration power (few cm in air
and a fraction of mm in body tissues).
 They have discrete energies typically 4MeV
(Megaelectron-volt).
Type of Radiation
Beta Particles
These have the following characteristics:
 They have the same mass as an electron.
 They may be charged negatively (negatron or
electron) or positively (positron); the former is most
common.
 Their penetration power is more (few meters in air
and a cm in body tissues)
 Beta particles are characterized by production of
particles with a continuous spectrum of energies
ranging from nearly zero to some maximum that is
characteristics for each decay process.
Type of Radiation
Gamma radiation
These have the following characteristics:
 This is similar to X-radiation but gamma radiation is emitted
from the nucleus in contrast of X-rays which are produced
from planetary electrons.
 When it reacts with matter, it behaves as if composed of
discrete packets (quanta) of energy. These are sometimes
called photons.
 Since it is an electromagnetic radiation, it has no mass or
charge and travels with the speed of light.
 It is very penetrating; high energy rays can pass through
several feet of solid matter.
 Gamma quanta have discrete energies, typically 2MeV
(Megaelectron-volt).
 Radioactive decay products
Alpha decay
 The α particle 2He4 (a helium nucleus) contains two protons and
two neutrons. α Particles are emitted by radioactive isotopes
(typically of mass numbers greater than approximately 150) as
they decompose to give daughter elements of lower atomic
masses. The decay of 92U238 to give 90Th234 is an example of such
as process:
92U →
238

90 Th + 2He
234 4

 Processes that give rise to and accompany α emissions proceed

via clearly defined mechanisms or pathways, which means that
the energy re-distributions that accompany these processes are
quantized. Energy releases via the emission of either X- or γ - rays
frequently accompany α particle decay processes.
Radioactive decay products
 α Particles are ejected from the decaying parent
nucleus with considerable kinetic energy (again
this is both quantifiable and predictable).This
kinetic energy is capable of causing considerable
ionization upon collision with the atoms or
molecules of many materials. α Particles
progressively lose energy upon each collision;
however, because of their relatively high mass,
they have a low capability for penetration and
may be typically stopped by a thick piece of
card. An α particle emitter can often be identified
by determining the path length over which the
particles travel (typically a few centimeters
through air).
Radioactive decay products
Beta decay
 There are three nuclear reactions that can be classified as β decay
processes and we shall consider each of these in turn. β Particles
are either electrons or positrons.
 The first of the β decay processes we shall consider involves the
capture of an electron by the nucleus, followed by the release of
an X-ray photon; this process is unfortunately of no analytical
significance.
 Both of the other two processes involve the ejection of an electron
or a positron from the nucleus (along with the formation of a
neutrino, v). In one of these processes, a neutron is converted into a
proton and an electron, which is subsequently expelled; an
example of this type of reaction is shown in following equation:
6C → 7N14 + β- + ¯ν
14
Radioactive decay products
 In the other process involving the formation of a positron,
β+ , the total number of protons within the nucleus
decreases by one, an example of which is shown in
following Equation:
30Zn → 29Cu65 + β+ + v
65

 Positrons are ultimately annihilated via reaction with an

electron and this is accompanied by the generation and
emission of two γ photons.
 Unlike α particles, β particles are generated with a
continuous range of kinetic energies. The penetrating
power of β particles far exceeds that of α particles due to
their vastly smaller mass. In practice, β particles can
typically penetrate up to several tens of centimeters of air,
with a minimum of a piece of aluminium foil normally being
required to stop radiation.
Radioactive decay products
Gamma-ray emission
 It should be realized that there is no difference
between X-rays and γ (gamma)-rays except that
X-rays are formed via electronic transitions,
whereas γ-rays originate from nuclear processes.
 Many α or β decompositions are accompanied by
the release of γ-rays as excited nuclei relax via
one or more quantized steps. In this way, the γ-rays
themselves have specific energies (frequencies)
and so can often be used in a fingerprinting
manner for identifying specific radioactive
decompositions.
Radioactive decay products
 γ-rays are highly penetrating with several centimeters of lead typically being
required as a shield. γ-rays lose energy and are stopped in this way via three
main mechanisms as they pass through matter. The mechanism that
predominates largely depends upon the frequency (and thus the energy) of
the γ-rays.
 For low-energy γ-rays, energy is largely lost via the photoelectric effect in
which the energy of a γ photon causes the excitation and displacement of
an electron from an atomic orbital within the material through which the
radiation passes. In most instances, the photon is entirely consumed so
stopping the radiation.
 For γ-rays of intermediate energy levels, the compton effect may be
observed as radiation passes through matter. Electrons are again displaced
from atomic orbitals although not all of the energy of the photon is
consumed, with the remainder of the energy continuing through the material
as a γ-ray of lower energy. In some instances, this can give rise to further
photoelectric or compton effects.
 Extremely highly energetic photons (>1.02 MeV) can sometimes be
completely absorbed in the vicinity of a nucleus via the formation of a
positron and an electron in a process known as pair production.
DETECTION AND
MEASUREMENT OF
RADIOACTIVITY
 The radioactivity of a substance can be detected and
even measured by the ionization of gases, caused by
alpha and beta particles. The following instruments are
used for this purpose:
 The Geiger Muller Counter: The apparatus consists of a
copper cylinder closed with a thin mica window at one
end. The cylinder is filled with an ionisable gas at a pressure
of about 10 mm of mercury. In the middle of the cylinder a
tungsten wire acts as an anode. The radioactive substance
is placed outside the tube, close to the window. As a single
alpha or beta particle (or gamma rays) enters the tube, it
causes ionization of the gaseous molecules. A momentary
flow of current takes place which can be easily amplified.
The current produces a flash of light in a neon tube and a
unit movement over a mechanical register.
DETECTION AND
MEASUREMENT OF
RADIOACTIVITY
 The Wilson Cloud Chamber: The apparatus consists of a
chamber with a glass window and is closed by a piston
which can be moved up or down. It is filled with dust free
air saturated with water vapour at saturation pressure. As
the particles enter through a window the air is made to
expand, the temperature falls and the vapours become
supersaturated. As a result a fog track deposits along the
path of the particles, which can easily be photographed.
This leads to the detection of these particles.
 Scintillation Method: This method is based on the fact that
when α particles emitted by radium are allowed to strike
against a fluorescent screen of zinc sulphide scintillation are
produced, each scintillation corresponding with one
particle. The screen is coupled to a photo multiplier to
convert scintillations into electric pulses which are amplified
and recorded.
Instrumentation
 Scintillation counters, gas-filled detectors and
semiconductor-based detectors can all be
used to measure radioactive events in a very
similar manner to the detection of X-rays since
α and β particles, along with γ photons, are
all ionizing forms of radiation. Each of these
three types of detector rely on the production
of photoelectrons upon absorption of
radiation and this can give rise to many ion
pairs in the form of a cascade, which
generates a measurable electrical pulse.
Instrumentation
Measurement of α particles
 Analyte samples that are known (or
suspected) to be α emitters are normally
prepared as thin film coatings upon a host
underlying material to minimize self-
absorption by the material, since as we have
seen, the penetrating power of α particles is
very small. α spectra consist of discrete peaks
that may be used for identification by using
pulse height analysers.
Instrumentation
Measurement of β particles
 Liquid scintillation counters are typically used for counting low-
energy β emitters such as S35, tritium or C14 with the sample typically
being dissolved in a solution of the scintillating compound that is
placed in a vial situated equidistant between two photomultiplier
tubes in a light proof housing. The output of the two counters is fed
to a coincidence counter that only registers a pulse when both
detectors record a signal simultaneously. In this way, background
noise associated with the detectors and amplifiers can be
significantly decreased, since it is unlikely that such effects would
influence both detectors simultaneously. Liquid scintillation
counting is one of the most widely used radiochemical analytical
approaches especially with clinical applications.
 Higher-energy β emissions can be counted using a well scintillation,
Geiger-Muller tube or proportional tube counter placed at a
suitable distance close to the source, which should normally be
prepared so as to have a flat planar surface.
Instrumentation
Measurement of γ photons
 γ-radiation is normally measured using Geiger
Muller tubes the ends of which are normally
protected by thin aluminium or Mylar windows so
as to filter out α or β background interferences. γ-
rays spectrophotometers are also often used for
identification of the emitting radioisotope(s)
according to the frequency of the radiation as
well as allowing for quantification of the number of
radioactive emissions in a given time according to
the number of photons received.
 Carbon14 dating
Carbon14 dating
 C14 dating is a very widely used technique for the dating of objects containing organic
matter derived from plant tissue. This approach allows dating of objects over time spans
of many thousands of years with applications ranging in paleontology (the study of fossils)
or the dating of historical objects such as fabrics derived from plant material such as
cotton or wool (e.g. used for the much publicized dating of the Turin shroud).
 C14 is formed in the atmosphere via the action of cosmic rays on CO2 within the upper
limits of the atmosphere. However, this isotope is unstable, possessing a half-life of 5568
years and decays via a β emission according to following equation:
6C
14 → N14 +
7
β- + ¯ν
 Radioactive C14 in CO2 becomes fixed within carbohydrates via photosynthesis. C14
fixation stops (and therefore the accumulation of radioactive 14CO2) when the plant
naturally dies or when it is eaten by an animal; in this way, the age of materials
incorporating plant derived material can be determined by radioactive counting in order
to quantify the percentage of radioactive C14: C12 within a sample.
Nuclear Fission
 In 1939, Hann and strassman observed that when uranium atom is
bombarded with neutron, it disintegrates into some products along with a few
neutrons and energy. This phenomenon in which a heavy nucleus breaks into
two or more products liberating huge amount of energy is called nuclear
fission. In other words, the process of splitting of heavy nucleus into a number
of fragments of much smaller mass, when bombarded with a suitable sub-
atomic particles are known as Nuclear Fission. The main fission products are
barium and krypton. e.g.
92U
235 + n1 → 56Ba141 + 36Kr92 + 3 Neutron +
0
Energy
 The energy is released according to Einstein energy mass relation i.e. E = m C2
and the process does not stop in one step, but it become a chain reaction.
The nuclear chain reaction of nuclear fission will not occur if:
 The mass of uranium is so small that neutron can easily and quickly escape
from it.
 The neutrons are too fast to be retained by the uranium mass.
 The uranium mass contains some strong neutron absorber.
Applications of Nuclear Fission
 The important application of nuclear fission are given
below:
 In the Formation of Atom Bomb: When two lumps of U235
are suddenly brought together, a rapid nuclear chain
reaction is setup resulting in an explosion. This is in brief the
principle of atomic bomb.
 As a Source of Nuclear Energy: The energy released during
the fission process can be used as generation of heat of
electric power.
 As a fuel for the purpose of engine in ship and submarine.
 As a Rocket fuel.
 In the production of isotopes from neutron induced
transmutation.
Nuclear Fussion
 A process in which lighter nuclei of atoms fuse together to form a heavier
nucleus with slightly less mass is known as nuclear fusion e.g.

1H + 1H2 → 2He4
2

1H + 1H3 → 2He4 + 0n1

2

 Or Nuclear fusion can also take place by accelerated protons and

deuteron to combine with lighter element. Such process occur at very high
temperature (of the order of a million °C), therefore they are also called
thermonuclear reaction. The nuclear fusion accounts for the very high
temperature prevailing on the sun. The energy of Sun is supposed to arise
from the following thermonuclear reactions e.g.

1H + 1H1 → 1H2 + 1e0 + energy

1

1He + 1H1 → 2He3 + energy

2

2He + 2He3 → 2He4 + 21H1 + energy

3
Nuclear Fussion
Significance of Nuclear Fusion
 The important significance of nuclear fusion
are given below:
 (A) Nuclear fusion processes are responsible
for the release of large amount of energy in
the form commonly known as “Hydrogen
Bomb”.
 (B) Deuterium available from natural water
may be a future source of energy through
fusion reaction
Difference between Nuclear
Fission and Nuclear Fusion

Nuclear Fission Nuclear Fusion

In this process a heavy nucleus In this process two or more lighter
splits into Lighter nuclei. nuclei combine to form the heavy
nucleius
It does not require high It requires extremely high
temperature. temperature.
It is a chain reaction. It is not a chain reaction.
The process can be controlled It cannot be controlled and
and the energy released can be energy released cannot be
used for peaceful purpose properly utilized.
The products formed are The products formed are non-
radioactive radioactive in nature.
RADIOPHARMACEUTICALS
 The substances or compounds which emit radiation and used in
medicine are known as radiopharmaceuticals. In other words, a
radiopharmaceutical product can be described as a special class
of radio isotopic product, a chemical formulation containing
radionuclide of adequate purity and safety suitable for internal
administration to humans or for performing a test in vitro for
medical purpose. The terms “Radioisotopes, radioactive isotopes
and radionuclide are used generally for substances which emit
ionizing radiation.
 Elements having the same atomic number but different atomic
weight or mass are called isotopes. This shows same chemical and
physical properties with a difference in the kinetics or rates of
reactions as it depends upon the mass.
They are classified into following two classes
 Stable Isotopes: They do not decompose into other isotopic form of
the element and do not emit radiations e.g. C12, CI35 etc.
 RADIOPHARMACEUTICALS
Unstable or Radioactive Isotopes: They decompose or decay by emitting the
nuclear particles into the other isotope or different elements. The phenomenon
of emitting radiations by these isotopes is known as radioactivity and such
isotopes are known as radioactive isotopes.
Types of Radionuclides
 They are mainly of two types:
 Natural Radionuclides: They are produce naturally.
 Artificial Radionuclides: They are produced in nuclear reactors in controlled
manner by reactor irradiation or cyclotron irradiation.
Radiopharmaceuticals can also be broadly classified into following two classes:
 Vivo Radiopharmaceuticals: They are administered into patients for
diagnosis or therapeutic applications.
 Vitro Radiopharmaceuticals: In vitro applications of radiopharmaceuticals
also include the radio-immunoassay (RIA) technique, other related
procedures (Immunoradiometric assay i.e. IRMA) and other assay based on
the principle of isotope dilution analysis.
Handling and Storage of
Radioactive Materials
 Great care must be taken in handling and storage of radioactive materials.
These materials are stored with the national and international regulations
concerning the storage of radioactive substance. During storage,
containers and solutions may darken due to the emitted radiation. Exposure
to radiation can lead several complicated disorders such as leukemia,
change in body pH, destruction of tissues etc. Therefore persons working
with radioisotopes should take certain precaution e.g.
 Radioactive materials should never be touched with hand but handled by
means of forceps or suitable instruments.
 Smoking, eating, drinking activities must not be carried out in the laboratory
where the radioactive materials are handled, since food contaminated
with radioactive material can damage internal organs.
 Radioactive materials should be kept in suitable labeled containers,
shielded by lead bricks and preferably in remote corner.
 Areas where radioactive materials are stored or used should be monitored,
that is continuously tested for radioactivity.
 There should be proper disposal of radioactive materials.
Applications of Radio isotopes
Radio isotopes are used in medicine for the following two
purposes
1. As source of radiation for radio therapy
 The treatment with γ radiation is given by focusing radiation
directly on the area under treatment and it is called
“teletherapy”. The therapeutic applications include the use
of open source in which radiation emitted, by their ability to
ionize atoms, produce destructive effect on existing cells
and prevent the formation of new cells and tissues. The
energy measurement involved in radiations and resulting in
ionization is expressed in mega electron volts called as
MeV. The radiations of short wavelength (gamma rays)
have high penetrating power than long wavelength (beta
rays). Besides the greater MeV of the rays, it becomes more
destructive to the surrounding tissues.
Applications of Radio isotopes
2. As radioactive tracers for diagnostic purpose
 The diagnostic application include scinitigraphy of
organs, both static and dynamic imaging and as
radioactive tracers. The static imaging study gives
the size and morphology of the organ under study,
whereas dynamic imaging study can be used for
studying the functioning of the organ. The high
detection sensitivity of radio isotopes makes them
ideal tracers. The prime requirement of a tracer and
its satisfactory distribution in an organ or system is its
ability to trace a particular metabolic or excretory
pathway, apart from this the product should be
suitable and safe for administration to humans.
Some Important Radio
isotopes
 Some important radio-isotopes used in medicine are given below:
 Carbon C14: It is the most important radio isotope used in various
studies e.g. In reaction mechanism, metabolism of carbohydrate
and fats, drug excretion, decomposition of pharmaceutical
products.
 Cobalt CO60: It is used in X-rays therapy, because it emits beta and
gamma rays. It is also used for the sterilization of surrounding
materials and dressing by gamma radiation.
 Cyanocobalamin CO57: It is a cyanocobalmin containing Co57. It is
used in the diagnosis of pernicious anemia.
 Ca44 and Ca45: It is used in the treatment of carcinoma of bone.
 H2 and H3: It is used in the determination of total body water.
 Gold (Au198) Solution: It is the colloidal solution of radioactive gold,
which emits beta and gamma rays. It is used in the estimation of
recticuloendothelial activity and as neoplastic suppressant.
Some Important Radio
isotopes
 Sodium Iodide (I131) Capsule and solution: It is a radioactive
isotope of iodine 131 in the form of sodium iodide 131. It
emits beta and gamma rays and mainly used as a
diagnostic and therapeutic agent in thyroid conditions and
in myxedema.
 Iron55 and Iron59: It emits beta and gamma radiations. It is
used to measure red cell life span. In addition to this, it is
also used in research studies about utilization and
absorption of iron salts.
 Sodium Chromate (Cr51) Solution: It is a radioactive
chromium 51 ion in the form of Na2Cr51O4. It is used to study
red cell volume and its survival time.
 Nitrogen (N13 and N15): It is useful in the investigation of
amino acids and protein metabolism. It is also used in the
studies of nitrogen fixation by plant.
Some Important Radio
isotopes
 Erbium (Er169): It is used as erbium citrate in the form of an injectable
suspension. It is used in the treatment of arthritic conditions of small
joints.
 Iodine (I131): It is the most important radioisotope of iodine which is
used in treating complaints regarding the function of thyroid gland.
Iodine is absorbed by thyroid gland to form the thyroxin hormone.
For detecting the defect of the thyroid gland, a known weight of
sodium iodide containing some I-131 is given to the patient. The
rate of absorption of radioiodine in the gland is accurately
determined by measuring the radioactivity in the gland using
suitable scintillation counters. The radioactivity may be high at a
particular region in the gland. Thus the hypersensitive part of the
gland can be located.
 I131 is also used in locating the position and to find the size of tumors
in the brain, since it is strongly absorbed by brain tumor.
Some Important Radio
isotopes
 Cobalt (Co-60): It is also used in the treatment of
cancerous tissue in the body. The isotope in the form
of thin wires or very thin disc can be used just at the
site of malignant tissues in the body to destroy the
unwanted tissue.
 Cobal-60 extends the storage life of many food
articles like meat and fruit. It is also used to detect or
find cracks and other defects in metal casting.
 Phosphorous (P-32): P-32 is used in the treatment of
chronic leukemia (abnormal increase in white blood
corpuscles) and polycythemia (abnormal increase in
red blood corpuscles) and increase in blood volume.
It is also used to find the rate at which phosphatic
fertilizers are absorbed by the plant from the soil.
Some Important Radio
isotopes
 Ferric citrate (Fe-59): It is a beta and gamma emitting isotope. It is
prepared by neutron activation of iron 58. The isotope is used in
diagnostic procedures which are related to various aspect of iron
metabolism and red blood cell formation. It finds use in the
investigation of haematological disorders.
 It is sold under the generic name Ferric Citrate and also the trade
name of Ferrutope. The usual oral and intravenous does have been
2 to 5 µc (microcoulomb) and may range as high as10 µc
(microcoulomb).
 Sodium phosphate (P-32): It emits beta particles. It has been found
to be suitable for used either as a sterile solution for injection or as
an oral solution. Intravenous administration usually needs about
75% of the oral dose. It has been found to be useful for both
diagnostic use for sodium phosphate and in the localization of
intraocular tumor. It is also used in the localization of cerebral
tumour. It is mainly used in the treatment of polycythemia vera, a
disease characterized by the increase in the number and absolute
mass of red blood cells.
Biological effects of radiations
or Hazards of radioactivity
 Radiations have dangerous effect on biological system. The
destructive effect of radioactivity is directly related to its
interaction with molecules present in the tissue to produce
abnormal ions. These chemical species change the local
pH or initiate free radical chain reactions forming peroxides
and other toxic compounds, causing necrosis and
destruction of the tissues or organ. These changes can be
noticed after a short period of time or may take years to
develop or as in the case of genetic changes. The effect of
radioactive particles depends on the following factors.
 The ability of the radiation to penetrate tissue.
 The energy of the radiation.
 The particular tissue and surface area exposed and
 The dose rate of radiation.
Biological effects of radiations
or Hazards of radioactivity
 Different types of radiation differ significantly in
their abilities to penetrate tissue. Alpha particles
have a potential to produce an excess amount of
free radicals. The range and penetration of these
particles are very low and would not penetrate
the surface even if they are very close to the skin.
But the ionizing power of gamma rays is relatively
low, their range and penetrating ability are quite
high to produce significant damage at distance
of several meter form the source. They collide with
atoms of the tissue and damage them.
Biological effects of radiations
or Hazards of radioactivity
 Water present in body forms free radicals
which abstract radicals from other molecules
and produce different type of potentially
toxic species. These species can set a hostile
environment for cells and tissue causing
necrosis and finally complete destruction of
tissue or organ. They change the DNA in cells
and form cross-linking between certain amino
acid in protein. Food contamination with
radio-active material can seriously affect the
internal organ.
Various hazards of radiation
exposure
 Induction of Cancer: Cancer is greatest risk in humans while
exposed to low levels radiations. The most common
cancers induced by radiation in humans are breast, thyroid
and lung cancer, in addition to this leukemia and
alimentary tract cancer is also observed. The survivors of
1945 Hiroshima and Nagasaki bomb blast are the best
example of cancer caused by radiation.
 Genetic Effects: Radiations are responsible for various
genetic effects. The genetic risk of cancer in humans is
mainly based upon animal studies, since there is no
significant demonstration of radiation induced gene
mutation in humans, thus the risk of a genetic defect in the
child of a patient who had undergone a diagnostic test
using radionuclides is insignificant.
Various hazards of radiation
exposure
 Effect on the Embryo: The developing embryo is very
sensitive to radiation. The major effect of high doses of
radiation may causes the death of embryo, malformation
and reduced growth. During the stage of gestation when
the organ systems are differentiating is most sensitive time
to determining the effects.
 During the period of organogenesis (about 11 to 50 days
after fertilization) congenital malformation and reduced
growth are the results of radiation damage. After
organogenesis (the fetal stage) growth retardation is the
major effect from high doses. For diagnostic procedures
the embryonic exposure is uniformly under 5 rads, at which
dose there is negligible risk. At doses above 15 rad, the risk
of malformation is significantly increased.
Various hazards of radiation
exposure
 Effect on Lactation: During lactation, the
use of radiopharmaceutical involves a risk
that a breast feeding child may receive
radioactivity secreted in breast milk.
Therefore a safe interval between
administration of radiopharmaceutical
and resumption of breast feeding should
be observed e.g. Tc-99m when
administered breast feeding should be
discontinued for 24 hours.
RADIOOPAQUE CONTRAST
MEDIA
 The substance or compound that have the property of causing a shadow
on X-ray films are known as Radioopaque substance. These substances
have the ability to stop the passage of X-rays and hence appear opaque
on X-ray examination. Such compounds and their preparation are called as
X-ray constrast media. All radiopaques are not radio-pharmaceutical unless
they contain a radio isotope in their structure or formula.
 X-rays are electromagnetic radiation of short wavelength and thus have
high penetration power. The electrons of high atomic number element can
interact with X-rays. The interaction causes interference in their passage
through the medium. X-rays are capable of passing through most soft tissues
and hence cause darkening on X-ray film. When a photographic film or a
photosensitive plate is placed opposite to the X-ray source through
patient’s body or organ portions, the film or plate is darkened in an amount
proportional to the number of X-rays that are able to pass.
RADIOOPAQUE CONTRAST
MEDIA
 As a general rule, capability of absorbing or stopping the passage of X-rays,
is directly proportional to availability of electrons in the system. Bones and
teeth contain element of high atomic number like calcium and
phosphorous cast shadow on film, they provide large localization of
electron density, on the other hand skin and soft tissues contain element of
low atomic number like hydrogen, nitrogen, oxygen and carbon, hence
they do not act as an enough or sufficiently dense electron barrier on
screen. Hence, on the basis of different composition of various tissues, the
capacity to absorb or block the passage of X-rays varies and therefore, it is
possible to have fair idea about the size and shape of various anatomical
organs upon visualization which produces shadow on X-ray exposed film or
plates. However, the difference is sometimes so little and overlapping that it
is not possible to make a correct diagnosis and may often lead to an
incorrect conclusion. The different anatomical organs containing a
radiopaque gives a much clear and distinguishing shadow on X-ray films or
plates for proper diagnosis and interpretations.
RADIOOPAQUE CONTRAST
MEDIA
 The most common contrast media contain iodine
or barium among various inorganic elements. Their
X-ray opacity is dependent upon their capacity to
provide adequate concentration in the specific
organ to be studied. Although they do not have
the highest atomic numbers, they are the most
easily incorporated into molecules exhibiting
relatively low toxicity. They become concentrated
in the organ to be studied, thus producing opacity
to X-rays and as contrast media in the diagnosis of
soft tissues by X-rays. The important inorganic
compound used as contrast media is barium
sulphate.
Barium Sulphate
BaSO4 Molecular weight = 233.4
 It is an important contrast media. In nature it occurs
in mineral barite or heavy spar from which is cannot
be easily purified. It contains not less than 97.5% of
BaSO4.
 Preparation: In laboratory it is prepared by adding
any soluble sulphate to a solution of any barium salt.
BaCI2 + H2SO4 → BaSO4 +
2HCI
 The salt is filtered off, washed thoroughly, dried in a
steam oven and screened.
Barium Sulphate
 Properties: It is a fine heavy white odourless bulky powder free from
gritty particles. It is in soluble in water and very stable towards heat
and reagents. It dissolves in hot concentrated suplhuric acid
forming barium acid sulphate Ba (HSO4)2.
 Test for Purity: Tests for phosphate, arsenic, copper, lead, mercury,
tin, zinc, heavy metals, sulphide, oxidizable suphur, acidity,
alkalinity, acid soluble substance, soluble barium salts, bulkiness or
sedimentation and loss on drying.
 For the determination of sulphide, acidifed solution of the salt
boiled with hydrochloric acid. Now exposed a lead acetate paper
to the vapour. If sulphide is present the paper become darker. For
detecting the presence of phosphate into the acidified solution of
the substance. If no yellow precipitate is formed it indicate the
presence of phosphate.
Barium Sulphate
 Acidity or alkalinity is determined by heating barium
sulphate with water. The solution is filtered and add
bromothymol blue into the filtrate. Now neutralized it with
0.01 N hydrochloric acid or 0.01 N sodium hydroxide.
 For determining acid soluble substances, acidified the
solution with the help of dilute hydrochloric acid and filter it.
The filtrate is evaporated, the residue dried and weighed.
The presence of soluble barium salt is find out by digesting
the residue obtained in the test for acid soluble substances
with water. The solution is filtered and add dilute sulphuric
aicd into the filtrate. Now keep the solution for 39 minutes,
no turbidity is produced.
 Bulkiness is determined by allowing to stand an aqueous
suspension of the substance in a graduated cylinder.
Barium Sulphate
Test for Identification
 A paste of barium salt with hydrochloric acid gives an apple green
colour to the Bunsen flame.
 The substance is boiled with sodium carbonate solution. Now dilute
it and filtered. The filtrate acidified with dilute hydrochloric acid. The
solution gives the reaction of sulphates.
 Assay: It is assayed by fusion of the known weight of compound
with sodium carbonate and potassium carbonate at 1000 °C for
fifteen minutes. It is cooled suspended in water and decanted. The
residue is washed with 2% sodium carbonate solution (until free
from sulphate). Now add dilute hydrochloric acid, ammonium
acetate, potassium dichromate and urea into the residue. The
suspension is digested at 80-85 °C for 16 hours and then filtered
through sintered glass crucible. The precipitate washed with
potassium dichromate and finally with water and dried at 105 °C
and weighed. 1.0 g of the residue is equivalent to 0.9213 g of
BaSO4.
Barium Sulphate
 Uses: It is used as a radioopaque contrast media for
the X-ray examination of the gastro intestinal tract. It
is insoluble in acidic gastric juice and hence does not
produce the systemic effects of soluble toxic barium
salt. It is administered by enema for examination of
the colon. The patient is usually given 30 ml caster oil
or other suitable cathartic before the examination.
While preparing barium sulphate mixtures, it should
be strained through gauze or mixed well with
otherwise lumps of salt may give a false indication of
an ulcer niche.
 After oral or rectal administration of barium sulphate,
constipation may occurs. Sometime it may causes
vomiting, diarrhea, hemorrhage, cardiac arrest etc.
Aluminium
Hydroxide
ALI ABBAS
M.Phil. Pharmaceutical
CHEMISTRY
Occurrence
 Aluminium hydroxide, Al(OH)3, is found in nature as the
mineral gibbsite (also known as hydrargillite) and its other much
rarer polymorphs: bayerite, doyleite, and nordstrandite.
Aluminium hydroxide is amphoteric in nature, i.e., it has
both basic and acidic properties. Closely related are aluminium
oxide hydroxide, AlO(OH), and aluminium oxide or alumina
(Al2O3), the latter of which is also amphoteric. These compounds
together are the major components of the
aluminium ore bauxite.
AL(OH) 3
It is studied under two headings.
 Aluminium Hydroxide Gel: It is an aqueous suspension of
hydrated aluminium oxide with varying amount of basic
aluminium carbonate. It contains not less than 3.5% W/V
and not more than 4.4% W/V of aluminium oxide. It
contains glycerin, sorbitol saccharine or sucrose as
sweating agent, oil of mentha or peppermint oil as
flavouring agent and sodium benzoate as preservative.
 Dried Aluminium Hydroxidel Gel: It is also known as
hydroxide powder or aluminium hydrate powder. It consists
mainly of hydrated aluminium oxide and varying amount of
basic aluminium carbonate and bicarbonate. It contains
not less than 47.0 % AI2O3 and not more than 60.0 % AI2O3.
Preparation
 Itis prepared by adding alkali hydroxide
or ammonia into an aluminium salt.
3 NH4OH + AICI3
AI (OH)3 + 3 NH4 CI
 On treating with dilute solution of sodium
hydroxide, the gelatinous precipitate is
converted to a crystalline form, which on
drying at 100 °C to give Al2O3 . 3H2O
Properties
 It is white odourless, tasteless amorphous powder.
It is insoluble in water and alcohol but soluble in
dilute mineral acids and in solution of alkali
hydroxide due to its amphoteric nature
AI (OH)3 + 3 HCI
AICI3 + 3H2O
AI (OH)3 + NaOH
NaAIO2 (Sodium aluminate) + 2H2O
 On strong heating, it changes to alumina.
Precipitated aluminium hydroxide adsorbs
colouring matter and colloidal substances.
Polymorphism
 Four polymorphs of aluminium hydroxide exist,
all based on the common combination of
one aluminium atom and
three hydroxide molecules into
different crystalline arrangements that
determine the appearance and properties of
the compound. The four combinations are:
1. Gibbsite
2. Bayerite
3. Nordstrandite
4. Doyleite
Polymorphism
 All polymorphs are composed of layers
of octahedral aluminium hydroxide units with the
aluminium atom in the Centre and
the hydroxyl groups on the sides, with hydrogen
bonds holding the layers together. The
polymorphism vary in how the layers stack
together, with the arrangements of the molecules
and layers determined by the acidity, presence
of ions (including salt). Under most conditions,
gibbsite is the most chemically stable form of
aluminium hydroxide. All forms of Al(OH)3 crystals
are hexagonal.
Assay
 It is assayed by complexometric titration method in terms
of their aluminium oxide content and their acid
consuming capacity. Accurately weighed amount of the
sample is dissolved in hydrochloric acid and diluted with
water. Now add standard known amount of disodium
EDTA water and methyl red solution into it. The mixture is
neutralized with 1N NaOH solution. Now the solution is
warmed and add hexamine. The access of disodium
EDTA is determined by titrating with standard lead nitrate
solution using xylenol orange as indicator. Each ml of 0.05
N disodium EDTA is equivalent to 0.002549 g of Al2O3.
Uses
 It is a gastric antacid. It buffers the gastric
acid and so raises the pH and reduces acid
induced damage. Dried aluminium hydroxide
gel is used externally as mild astringent and
desiccant.
 It is used as a phosphate binder in patients
with chronic renal failure and as an adjuvant
in the manufacture of adsorbed vaccines. It
has astringent and demulcent properties by
which it forms a protective coating over the
ulcer crater. It is also used in antiperspirants
and dentifrices. It may also absorb toxins.
Uses
 Precipitated aluminium hydroxide is included as
an adjuvant in some vaccines (e.g. anthrax
vaccine). One of the well-known brands of
aluminium hydroxide adjuvant is Alhydrogel,
made by Brenntag Biosector. Since it absorbs
protein well, it also functions to stabilize vaccines
by preventing the proteins in the vaccine from
precipitating or sticking to the walls of the
container during storage.
 Aluminium hydroxide also finds use as a fire
retardant filler for polymer applications in a similar
way to magnesium hydroxide and mixtures
of huntite and hydromagnesite.
Ammonium
Chloride
ALI ABBAS
M.Phil. Pharmaceutical
CHEMISTRY
Occurance
 Ammonium chloride is an inorganic compound with the formula
NH4Cl and a white crystalline salt that is highly soluble in water.
Solutions of ammonium chloride are mildly acidic. Sal
ammoniac is a name of the natural, mineralogical form of
ammonium chloride.
 Ammonium chloride occurs naturally in volcanic regions, forming
on volcanic rocks near fume-releasing vents (fumaroles). The
crystals deposit directly from the gaseous state and tend to be
short-lived, as they dissolve easily in water.
Properties
1.It occurs as a white or colourless crystalline or a
coarse powder. It is almost odourless and has a
cooling saline taste. It sublimes without melting. It is
freely soluble in water and glycerol and sparingly
soluble in alcohol. Its freshly prepared aqueous
solution are neutral to litmus but become quickly
acidic on standing due to hydrolysis.
NH4Cl + 2H2O → NH4OH + H3O+
+ Cl-
 Ammonium chloride solutions are incompatible
with alkalies, carbonate of alkaline earth and lead
salts.
Properties
2. Ammonium chloride appears to sublime upon heating but
actually decomposes into ammonia and hydrogen
chloride gas
NH4Cl → NH3 + HCl
3. Ammonium chloride reacts with a strong base, like sodium
hydroxide, to release ammonia gas
NH4Cl + NaOH → NH3 + NaCl + H2O
4. Ammonium chloride also reacts with alkali metal carbonates
at elevated temperatures, giving ammonia and alkali metal
chloride
2 NH4Cl + Na2CO3 → 2 NaCl + CO2 +
H2O + 2 NH3
5. A 5 % by weight solution of ammonium chloride in water has
a pH in the range 4.6 to 6.0
Preparation
 Itis a product of the Solvay process used
to produce sodium carbonate
CO2 + 2 NH3 + 2 NaCl +
H2O → 2 NH4Cl + Na2CO3
 Commercially it is prepared by the action
of ammonia gas with hydrochloric acid.
NH3 + HCI ---------- NH4CI
 The product is purified by sublimation from
an iron vessel or by recrystallization.
Uses
1. The dominant application of ammonium chloride is as
a nitrogen source in fertilizers (corresponding to 90% of the
world production of ammonium chloride) such as
chloroammonium phosphate. The main crops fertilized this way
are rice and wheat in Asia.
2. Ammonium chloride is used as an expectorant in cough
medicine. Its expectorant action is caused by irritative action
on the bronchial mucosa, which causes the production of
excess respiratory tract fluid, which presumably is easier to
cough up. Ammonium salts are an irritant to the gastric
mucosa and may induce nausea and vomiting.
3. Ammonium chloride is used as a diuretic and systemic
acidifying agent. It is used in the treatment of severe
metabolic alkalosis to maintain the urine at an acid pH, in the
treatment of some urinary tract disorders.
Uses
4. Electrolyte Replacement Therapy
 In case of excess loss of water and electrolyte, fever, severe
vomiting and diarrhoea, we used electrolyte replacement
therapy. Generally we use following two types of solutions
in replacement therapy.
 a solution for rapid initial replacement
 a solution for subsequent replacement
 Commercially a number of electrolyte combination with
varying concentration are present in market as dry powder
or oral electrolyte solution which contains anhydrous
glucose (or glucose), sodium chloride, potassium chloride
and either sodium bicarbonate or sodium citrate. They also
contain a flavouring agent and a suitable agent for free
flow of the powder.
Uses
(a) Oral Rehydration Salt (Electral)
 It contain sodium chloride, potassium chloride, sodium
citrate, anhydrous dextrose and excipients. On dissolving a
packet of 35 gm in 1 litre of water, provided electrolyte
(mEq/l) as sodium (51) potassium (20), chloride (41), citrate
(30) and dextrose (150). After dilution the packet should be
used within 24 hours. It is used in case of diarrhea, vomiting,
muscle weakness and muscle cramps etc.
Oral Rehydration Home made Solutions
 It is prepared with the help of 40 gm sucrose (cane sugar),
5 gm table salt (NaCI) with or without a lemon squeezed in
one litre of water.
 Once the hydration has been achieved, ORS with lower
concentration of sodium will sufficient for the maintenance
needs of fluid and electrolytes.