EUROPEAN PHARMACOPOEIA 8.

2.2.36. Ionic concentration (ion-selective electrodes)

the required volumes (unless masses are specied) of the

individual components, followed by mixing. Alternatively, the
solvents may be delivered by individual pumps controlled by
proportioning valves by which mixing is performed according
to the desired proportion. Solvents are normally degassed
before pumping by sparging with helium, sonication and/or
using on-line membrane/vacuum modules to avoid the
creation of gas bubbles in the detector cell.
Solvents for the preparation of the mobile phase are normally
free of stabilisers and, if an ultraviolet detector is employed,
are transparent at the wavelength of detection. Solvents
and other components employed are to be of appropriate
quality. Adjustment of the pH, if necessary, is effected using
only the aqueous component of the mobile phase and not
the mixture. If buffer solutions or saline solutions are used,
adequate rinsing of the system is carried out with a mixture of
water and a small proportion of the organic part of the mobile
phase (5 per cent V/V) to prevent crystallisation of salts after
completion of the analysis.
Mobile phases may contain other components, e.g. a
counter-ion for ion-pair chromatography or a chiral selector
for chromatography using an achiral stationary phase.
DETECTORS
Ultraviolet/visible (UV/Vis) spectrophotometers, including
diode array detectors, are the most commonly employed
detectors. Fluorescence spectrophotometers, differential
refractometers (RI), electrochemical detectors (ECD), light
scattering detectors, charged aerosol detectors (CAD), mass
spectrometers (MS), radioactivity detectors or other special
detectors may be used.

Ci

= molar concentration of the ion,

= the activity coefcient

If :
S

and
= slope of the calibration curve of the electrode,

the following holds :

and for
:
.
The potentiometric determination of the ion concentration is
carried out by measuring the potential difference between two
suitable electrodes immersed in the solution to be examined ;
the indicator electrode is selective for the ion to be determined
and the other is a reference electrode.
Apparatus. Use a voltmeter allowing measurements to the
nearest 0.1 millivolt and whose input impedance is at least one
hundred times greater than that of the electrodes used.
Ion-selective electrodes may be primary electrodes with a
crystal or non-crystal membrane or with a rigid matrix (for
example, glass electrodes), or electrodes with charged (positive
or negative) or uncharged mobile carriers, or sensitised
electrodes (enzymatic-substrate electrodes, gas-indicator
electrodes). The reference electrode is generally a silversilver
chloride electrode or a calomel electrode, with suitable
junction liquids producing no interference.
Procedure. Carry out each measurement at a temperature
constant to 0.5 C, taking into account the variation of the
slope of the electrode with temperature (see Table 2.2.36.-1).
METHOD
Adjust the ionic strength and possibly the pH of the solution
to be analysed using the buffer reagent described in the
Equilibrate the column with the prescribed mobile phase
monograph and equilibrate the electrode by immersing it in
and ow rate, at room temperature or at the temperature
specied in the monograph, until a stable baseline is achieved. the solution to be analysed, under slow and uniform stirring,
until a constant reading is obtained.
Prepare the solution(s) of the substance to be examined and
the reference solution(s) required. The solutions must be free
Table 2.2.36.-1. Values of k at different temperatures
from solid particles.
Temperature (C)
k
Criteria for assessing the suitability of the system are described
20
0.0582
in the chapter 2.2.46. Chromatographic separation techniques.
The extent to which adjustments of parameters of the
25
0.0592
chromatographic system can be made to satisfy the criteria of
system suitability are also given in this chapter.
30
0.0602
If the electrode system is used frequently, check regularly the
01/2008:20236 repeatability and the stability of responses, and the linearity
corrected 8.3 of the calibration curve or the calculation algorithm in the
range of concentrations of the test solution ; if not, carry out
2.2.36. POTENTIOMETRIC
the test before each set of measurements. The response of
the electrode may be regarded as linear if the slope S of the
DETERMINATION OF IONIC
calibration curve is approximately equal to k/zi, per unit of pCi.

CONCENTRATION USING
ION-SELECTIVE ELECTRODES

Ideally, the potential E of an ion-selective electrode varies

linearly with the logarithm of the activity ai of a given ion, as
expressed by the Nernst equation :

E0
R

= part of the constant potential due to the apparatus

used,
= gas constant,

= absolute temperature,

F
zi

= Faradays number,
= charge number of the ion including its sign.

At a constant ionic strength, the following holds :

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METHOD I (DIRECT CALIBRATION)

Measure at least three times in succession the potential of
at least three reference solutions spanning the expected
concentration of the test solution. Calculate the calibration
curve, or plot on a chart the mean potential E obtained against
the concentration of the ion to be determined expressed as
log10 Ci or pCi.
Prepare the test solution as prescribed in the monograph ;
measure the potential three times and, from the mean
potential, calculate the concentration of the ion to be
determined using the calibration curve.
METHOD II (MULTIPLE STANDARD ADDITIONS)
Prepare the test solution as prescribed in the monograph.
Measure the potential at equilibrium ET of a volume VT of
this solution of unknown concentration CT of the ion to be
determined. Make at least three consecutive additions of
a volume VS negligible compared to VT (VS 0.01VT) of a
reference solution of a concentration CS known to be within
the linear part of the calibration curve. After each addition,
See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 8.3

2.2.36. Ionic concentration (ion-selective electrodes)

measure the potential and calculate the difference of potential METHOD III (SINGLE STANDARD ADDITION)
E between the measured potential and ET. E is related to
the concentration of the ion to be determined by the equation : To a volume VT of the test solution prepared as prescribed
in the monograph, add a volume VS of a reference solution
containing an amount of the ion to be determined known to
give a response situated in the linear part of the calibration
curve. Prepare a blank solution in the same conditions.
Measure at least three times the potentials of the test solution
or
and the blank solution, before and after adding the reference
solution. Calculate the concentration CT of the ion to be
analysed using the following equation and making the
necessary corrections for the blank :
VT

= volume of the test solution,

CT

= concentration of the ion to be determined in the

test solution,
= added volume of the reference solution,

VS
CS
S

= concentration of the ion to be determined in the

reference solution,
= slope of the electrode determined experimentally,
at constant temperature, by measuring the
difference between the potentials obtained with
two reference solutions whose concentrations
differ by a factor of ten and are situated within the
range where the calibration curve is linear.

Plot on a graph
(y-axis) against VS (x-axis) and
extrapolate the line obtained until it intersects the x-axis.
At the intersection, the concentration CT of the ion to be
determined in the test solution is given by the equation :

General Notices (1) apply to all monographs and other texts

VT

= volume of the test solution or the blank,

CT

= concentration of the ion to be determined in the

test solution,
= added volume of the reference solution,

VS
CS
E
S

= concentration of the ion to be determined in the

reference solution,
= difference between the average potentials measured
before and after adding VS,
= slope of the electrode determined experimentally,
at constant temperature, by measuring the
difference between the potentials obtained from
two reference solutions whose concentrations
differ by a factor of ten and are situated within the
range where the calibration curve is linear.

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