EUROPEAN PHARMACOPOEIA 10.0
Potentiometric titration
Calculate the corrected mean temperature (T2) using the
following expression :
T1 - F
T1 = mean drop point temperature of 3 samples, in °C ;
F = compensation for the difference in temperature
between the sample and the point in the heating
block where the temperature is measured ; this will
vary depending upon the design of the automatic
drop point instrument and is provided by the
manufacturer.
Taking into account the drop point of the certified reference
material (T0), the accuracy of the temperature scale is
satisfactory if |T2 − T0| is not greater than 0.3 °C.
01/2008:20218
2.2.18. FREEZING POINT
The freezing point is the maximum temperature occurring
during the solidification of a supercooled liquid.
Figure 2.2.18.-1. – Apparatus for the determination of freezing
point
Dimensions in millimetres
Apparatus. The apparatus (see Figure 2.2.18.-1) consists of a
test-tube about 25 mm in diameter and 150 mm long placed
inside a test-tube about 40 mm in diameter and 160 mm
long. The inner tube is closed by a stopper which carries a
thermometer about 175 mm long and graduated in 0.2 °C
fixed so that the bulb is about 15 mm above the bottom of the
tube. The stopper has a hole allowing the passage of the stem
of a stirrer made from a glass rod or other suitable material
formed at one end into a loop of about 18 mm overall diameter
at right angles to the rod. The inner tube with its jacket is
supported centrally in a 1 L beaker containing a suitable
cooling liquid to within 20 mm of the top. A thermometer is
supported in the cooling bath.
General Notices (1) apply to all monographs and other texts
2.2.20.
Method. Place in the inner tube sufficient quantity of the
liquid or previously melted substance to be examined, to cover
the thermometer bulb and determine the approximate freezing
point by cooling rapidly. Place the inner tube in a bath about
5 °C above the approximate freezing point until all but the last
traces of crystals are melted. Fill the beaker with water or a
saturated solution of sodium chloride, at a temperature about
5 °C lower than the expected freezing point, insert the inner
tube into the outer tube, ensuring that some seed crystals are
present, and stir thoroughly until solidification takes place.
Note the highest temperature observed during solidification.
01/2016:20219
2.2.19. AMPEROMETRIC TITRATION
In an amperometric titration, the end-point is determined
by following the variation of the current measured between
2 electrodes (either one indicator electrode and one reference
electrode or 2 indicator electrodes) immersed in the solution
to be examined and maintained at a constant potential
difference as a function of the quantity of titrant added.
The potential of the measuring electrode is sufficient to ensure
a diffusion current for the electroactive substance.
Apparatus. The apparatus comprises an adjustable voltage
source and a sensitive microammeter ; the detection system
generally consists of an indicator electrode (for example, a
platinum electrode, a rotating-disc electrode or a carbon
electrode) and a reference electrode (for example, a silver-silver
chloride electrode).
A three-electrode apparatus is sometimes used, consisting of
an indicator electrode, a reference electrode and a polarised
auxiliary electrode.
Method. Set the potential of the indicator electrode as
prescribed and plot a graph of the initial current and the
values obtained during the titration as functions of the
quantity of titrant added. Add the titrant in not fewer than
3 successive quantities equal to a total of about 80 per cent
of the theoretical volume corresponding to the presumed
equivalence point. The 3 values must fall on a straight line.
Continue adding the titrant beyond the presumed equivalence
point in not fewer than 3 successive quantities. The values
obtained must fall on a straight line. The point of intersection
of the 2 lines represents the end-point of the titration.
For amperometric titrations with 2 indicator electrodes, the
whole titration curve is recorded and used to determine the
end-point.
01/2016:20220
2.2.20. POTENTIOMETRIC TITRATION
In a potentiometric titration (volumetric titration with
potentiometric end-point determination) the end-point
is determined by recording the variation of the potential
difference between 2 electrodes (either 1 indicator electrode
and 1 reference electrode, or a combined electrode) immersed
in the solution to be examined as a function of the volume
of titrant added.
Apparatus. The apparatus used comprises a millivoltmeter.
Commercial autotitrator instruments may be used and are
operated in accordance with the manufacturer’s instructions,
using electrodes recommended for the type of titration
described.
35
2.2.21. Fluorimetry EUROPEAN PHARMACOPOEIA 10.0

The indicator electrode to be used depends on the substance cx = concentration of the solution to be examined,
to be determined and may be a glass or metal electrode cs
(e.g. platinum, gold or silver). = concentration of the standard solution,
Ix = intensity of the light emitted by the solution to be
For acid-base titrations, a glass-silver-silver chloride electrode examined,
combination is generally used. Is = intensity of the light emitted by the standard
solution.
Method. Prepare the sample solution as described. Add If the intensity of the fluorescence is not strictly proportional
the titrant in suitable aliquots paying particular attention to the concentration, the measurement may be effected using
to the rate of addition and the volume increments near the a calibration curve.
end-point. Continue the titration beyond this point to allow a
clear detection of the end-point. In some cases, measurement can be made with reference
to a fixed standard (for example a fluorescent glass or a
solution of another fluorescent substance). In such cases,
The end-point of the titration is reached when the maximum the concentration of the substance to be examined must be
change in potential occurs in a plot of potential versus determined using a previously drawn calibration curve under
volume of titrant, and is expressed as the corresponding the same conditions.
volume of titrant. Recording the first or second derivative
curve can facilitate the determination of the end-point.
In potentiometric titrations of weak acids or bases using
non-aqueous solvents, if necessary, either carry out a blank 01/2008:20222
determination or pre-neutralise the solvent mixture. Where
it is impracticable to use potentiometric detection for this
purpose, the solvent mixture can be pre-neutralised by
titration using a suitable indicator. Some examples are given
below :
2.2.22. ATOMIC EMISSION
SPECTROMETRY
Titrant Indicator GENERAL PRINCIPLE
Perchloric acid Crystal violet solution R Atomic emission is a process that occurs when electromagnetic
radiation is emitted by excited atoms or ions. In atomic
3 g/L solution of thymol blue R emission spectrometry the sample is subjected to temperatures
Tetrabutylammonium hydroxide
in methanol R high enough to cause not only dissociation into atoms, but
also to cause significant amounts of collisional excitation
Ethanolic sodium hydroxide Thymolphthalein solution R
and ionisation of the sample atoms to take place. Once the
atoms and ions are in the excited states, they can decay to
lower states through thermal or radiative (emission) energy
01/2008:20221 transitions and electromagnetic radiation is emitted. An
emission spectrum of an element contains several more lines
than the corresponding absorption spectrum.
Atomic emission spectrometry is a technique for determining
the concentration of an element in a sample by measuring the
2.2.21. FLUORIMETRY intensity of one of the emission lines of the atomic vapour of
Fluorimetry is a procedure which uses the measurement of the the element generated from the sample. The determination is
intensity of the fluorescent light emitted by the substance to carried out at the wavelength corresponding to this emission
be examined in relation to that emitted by a given standard. line.
Method. Dissolve the substance to be examined in the solvent In this chapter only atomisation in flame is dealt with. The
or mixture of solvents prescribed in the monograph, transfer method of inductively coupled plasma-atomic emission
the solution to the cell or the tube of the fluorimeter and spectrometry (ICP-AES) is described in a different general
illuminate it with an excitant light beam of the wavelength chapter.
prescribed in the monograph and as near as possible APPARATUS
monochromatic.
This consists essentially of :
Measure the intensity of the emitted light at an angle of 90°
to the excitant beam, after passing it through a filter which – a sample introduction and nebulisation system ;
transmits predominantly light of the wavelength of the – a flame to generate the atoms to be determined ;
fluorescence. Other types of apparatus may be used provided – a monochromator ;
that the results obtained are identical.
– a detector ;
For quantitative determinations, first introduce into the
apparatus the solvent or mixture of solvents used to dissolve – a data-acquisition unit.
the substance to be examined and set the instrument to zero. Oxygen, air and a combustible gas such as hydrogen, acetylene,
Introduce the standard solution and adjust the sensitivity propane or butane may be used in flames. The atomisation
of the instrument so that the reading is greater than 50. If source is critical, since it must provide sufficient energy to
the second adjustment is made by altering the width of the excite and atomise the atoms. The atomic spectra emitted
slits, a new zero setting must be made and the intensity of from flames have the advantage of being simpler than those
the standard must be measured again. Finally introduce the emitted from other sources, the main limitation being that the
solution of unknown concentration and read the result on the flames are not powerful enough to cause emission for many
instrument. Calculate the concentration cx of the substance in elements allowing their determination. Acidified water is the
the solution to be examined, using the formula : solvent of choice for preparing test and reference solutions,
although organic solvents may also be used if precautions are
Ixcs taken to ensure that the solvent does not interfere with the
cx =
Is stability of the flame.

36 See the information section on general monographs (cover pages)