Utilization of ion-associate formation in conductimetric determi-
nation of some antihistamines in pharmaceutical formulations
Ahmed F. A. Youssef* and Raafat A. Farghali
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.
Received: June 25, 2006
Abstract
A simple and reliable titrimetric method has been
developed for determination of some antihistamine
compounds, namely cetirizine hydrochloride (CTZ.
Cl), hydroxyzine hydrochloride (HDZ.Cl) and
diphenhydramine hydrochloride (DPH.Cl). The method
is based on the titration of these compounds with
phosphotungestic (PT), phosphomolybdic (PM) and
silicomolybdic (SM) acids. The endpoint was located by
conventional and first derivative conductimetric methods.
The data were further treated by using Boltezmann
sigmoid method, where more sharp endpoints were
obtained. The method allowed the determination of CTZ.
Cl, HDZ.Cl and DPH.Cl within the ranges 5.13-30.78,
2.07-16.56 and 1.47-11.74 mg using PT acid, 5.13-25.65,
2.07 - 16.56 and 1.47-11.74 mg using PM acid and 5.13-
25.65, 2.07-16.56 and 2.93-11.74 mg using SM acid,
respectively. The method was further applied successfully
to some dosage forms containing these compounds, and
the results obtained were compared favourably with
those obtained using the pharmacopoeial methods. The
results were validated statistically and by using standard
addition technique through recovery.
Keywords: Cetirizine hydrochloride, hydroxyzine hy-
drochloride, diphenhydramine hydrochloride, conducti-
metric titration, phosphotungestic acid, phosphomolyb-
dic acid, silicomolybdic acid, heteropoly acids
*
Author to whom correspondence should be addressed:
e-mail: ayoussef@chem-sci.cu.edu.eg
Volume 51, No. 6, 2006
Accepted (in revised form): September 7, 2006
Résumé
Nous avons développé une méthode titrimétrique
simple et fiable pour la détermination de certains
composés antihistaminique, tels l’hydrochlorure de
cétirizine (CTZ.Cl), l’hydrochlorure d’hydroxyzine
(HDZ.Cl) et l’hydrochlorure de diphénhydramine
(DPH.Cl). La méthode est basée sur le titrage de ces
composés par les acides phosphotungstétique (PT),
phosphomolybdique (PM) et silicomolybdique (SM).
Le point équivalent a été localisé par les méthodes
conductimétriques conventionnelles et celles de la dérivé
première. Les données ont par la suite été traitées en
utilisant la méthode sigmoïde de Boltezmann, grâce
à laquelle des points équivalents mieux définis ont été
obtenus. La méthode a permis la détermination de CTZ.
Cl, HDZ.Cl et DPH.Cl dans des gammes de 5.13-30.78,
2.07-16.56 et 1.47-11.74 mg avec l’acide PT, 5.13-
25.65, 2.07 - 16.56 et 1.47-11.74 mg avec l’acide PM,
et 5.13-25.65, 2.07-16.56 et 2.93-11.74 mg avec l’acide
SM, respectivement. La méthode a, par la suite, été
appliquée avec succès à des mélanges pharmaceutiques
contenant ces composés et les résultats obtenus se sont
comparés favorablement avec ceux obtenus par les
méthodes de pharmacopée. Les résultats ont été validés,
statistiquement et par des études de recouvrement grâce
à la technique de l’ajout dosé.
Introduction
Drugs play a vital role in the progress of human
civilization by curing diseases. Today, a majority of the
drugs used are of synthetic origin. These are produced
in bulk and used for their therapeutic effects in phar-
Ion-associate formation in conductimetric determination of some antihistamines 289
maceutical formulations. There are biologically active
chemical substances generally formulated into conve-
nient dosage forms such as tablets, capsules, suspensions,
ointments and injection. These formulations deliver the
drug substances in a stable, non-toxic and acceptable
form, ensuring its bio-availability and therapeutic ac-
tivity (1). The wide spread adulteration and/or dilution
of commercially available pharmaceutical preparation
demand reliable methods for drug determination that are
preferably selective, rapid, and can be undertaken with
simple equipment.
Hydroxyzine hydrochloride (HDZ.Cl) [2192-20-3],
Figure 1, or (RS)-2-[2-[4-[(4-chlorophenyl) phenyl-
methyl] piperazin-1-yl]ethoxy] ethanol hydrochloride is
a piperazine derivative which is a rapid anxiolytic used
principally as an antiemetic (2). Few papers have been
reported concerning the determination of HDZ.Cl in
pharmaceutical preparations. These procedures include
direct and indirect titrimetric methods using ammonium
molybdate (3) and ethylenediaminetetraacetic acid
(EDTA) (4), where the endpoints were located conduc-
timetrically and visually using Eriochrome black T as
indicator, respectively. The pharmacopoeia method is Figure. 1. Chemical structures (A) Cetirizine hydrochloride (CTZ.Cl),
based on the potentiometric titration of HDZ.Cl in non- (B) Hydroxyzine hydrochloride (HDZ.Cl) and (C) Diphenhydramine
aqueous medium using perchloric acid (5). hydrochloride (DPH.Cl).
Cetirizine hydrochloride (CTZ.Cl) [83881-52-1],
Figure 1, is a piperazine derivative and carboxylated
them are either cumbersome or time consuming, or
metabolite of hydroxyzine. It is used in the treatment
involve the use of expensive equipment and reagents.
of perennial and seasonal allergetic rhinitis and also for
On the other hand, titrimetry is the simplest analytical
chronic uticaria. Literature mentions a few publications
techniques extensively used in the drug standardization
for determination of CTZ.Cl. These methods include
laboratories. Nevertheless, a number of titrimetric assay
spectrophotometry (6-10), fluorometry (11), ion selec-
methods can be found in different pharmacopoeias for
tive electrodes (12), titrimetry (10), LC (13) and HPLC
the routine analysis of different types of drugs in phar-
(9, 14-16).
maceutical dosage forms due to their cost-effectiveness
Diphenhydramine hydrochloride (DPH.Cl) [147-
as well as their ease of use. Therefore, the aim of the
24-0], Figure 1, is an antihistamine with antimuscarinic
present work is to develop a new reliable method as a
and pronounced sedative properties. It is also used as
continuation of our studies related to conductimetric
an antiemetic (2). It is usually given orally in as tablets,
titration (29, 30). The proposed conductimetric titration
capsules, or syrups. It may be administered by intramus-
yields accurate and reproducible results. These results
cular or intravenous injection in severe allergies and ap-
were validated statistically and through recovery studies.
plied topically for local allergic reactions in preparations
The method was applied successfully to pharmaceutical
of lotions and creams containing 1-2% (2,17). Several
formulations. In addition, the present work suggests the
methods have been proposed for assaying of DPH.Cl in
use of the Boltezmann sigmoid method (31) for endpoint
pure form and in pharmaceutical preparations. Of these
detection. This method has never been used in conduc-
methods, ion-association titration (18), ion selective
timetric determination of pharmaceutical compounds,
electrodes (19-21), flow injection spectrophotometry
although sharper endpoints are obtained upon treatment
(22), LC (23-25), GC (26), HPLC (27) and capillary
of the data with this method.
electrophoresis (28) have been used.
An inspection of most of the available methods for
the three above mentioned drugs reveals that most of

Canadian Journal of Analytical Sciences and Spectroscopy

290 Ahmed F. A. Youssef and Raafat A. Farghali
Experimental
Apparatus
A Hanna (Italy) conductivity meter model HI 9032
with a dip type cell (Kcell = 1.0) was used for conductivity
measurements. The bridge was connected with a ther-
mocouple for temperature measurements. A circulating
thermostat model Techne-C100 with a double jacket
cell was used to control the temperature of the measured
solutions.
Materials and reagents
Double-distilled water and analytical grade reagents
were used to prepare all solutions. Stock standard solu-
tions, 10-1 M, of cetirizine hydrochloride (Amriya for
Pharmaceutical Industries, Alexandria, Egypt), hydroxy-
zine hydrochloride (Chemical Industries Development,
Giza, Egypt) and diphenhydramine hydrochloride
(Pharaonia Pharmaceuticals Company, Alexandria,
Egypt) were prepared and stored in dark bottles. Work-
ing solutions of lower concentrations were invariably
prepared by appropriate dilution.
The following commercial formulations were sub-
jected to analysis by the proposed procedures: (i) Sultan
Capsules, labelled to contain 50 mg DPH·Cl/capsule
(Pharaonia Pharmaceuticals Company, Alexandria,
Egypt). (ii) Histazine-1 Syrup and tablets, labelled to
contain 1 mg CTZ.Cl/ml and 10 mg CTZ.Cl/tablet,
respectively (Amriya for Pharmaceutical Industries,
Alexandria, Egypt). (iii) Synthetic tablets containing
10 mg of HDZ.Cl/tablet. These tablets were prepared
in the laboratory.
Standard solutions, 10-2 M, of the reagents PT, PM
and SM acids (Aldrich, USA) were prepared by dissolv-
ing the required amounts of the pure solids in double-
distilled water.
General Procedure
A volume containing 1.02-30.78, 2.07-16.56 and
1.47-11.74 mg of CTZ.Cl, HDZ.Cl and DPH.Cl, re-
spectively, were transferred to a 50 ml volumetric flask
and made up to the mark with double-distilled water.
The contents of the volumetric flask were transferred to
a titration cell and the conductivity cell was immersed.
10-3 or 10-2 M solution of PT, PM or SM acids was then
added from a microburette and the conductance was
measured subsequent to each addition of the reagent
solution, after thorough stirring. The conductance read-
ing, taken 60 sec. after each addition, was corrected for
dilution (32). This correction can be minimized by using
Volume 51, No. 6, 2006
a titrant that is much more concentrated than the sample
solution. In the present study, the titrant is 10 times more
concentrated than the analyte.
A graph of corrected conductivity versus the volume
of added titrant was constructed and the endpoint was
determined.
Analysis of pharmaceutical formulations
Ten tablets were weighed and pulverized. A weighed
portion of the powder equivalent to 50 mg of cetirizine
hydrochloride was transferred into a 50 ml measuring
flask and shaken well for 5 min. The total volume was
adjusted to the mark with double-distilled water, mixed
and filtered. Different volumes of this solution, within
the application limits, were proceeded as described ear-
lier. The same procedure was followed for hydroxyzine
synthetic tablets, but the mass of only two tablets (20
mg) was used for analysis.
For the analysis of capsules, the content of ten Sultan
capsules (50 mg DPH.Cl/capsule) were mixed well and a
quantity of the resultant powder equivalent to 50 mg of
the drug was accurately weighed and transferred into a
50 ml measuring flask. The total volume was completed
to the mark with double-distilled water and then different
volumes of this solution were proceeded as described in
the general procedure.
For the analysis of syrup, the requested volume (3.0-
6.0 ml) of Histazine-1 syrup (1 mg CTZ.Cl/ml) was
transferred to a 50 ml measuring flask, completed to the
mark with double-distilled water and then proceeded as
described earlier.
Results and Discussion
The conductance titration of substances is possible
if a reaction occurs in which one ion is substituted for a
second ion of different mobility before the equivalence
point. The conductance method is well suited for the
determination of the endpoints in precipitation titrations,
where the shape of the titration curve can be predicted
by summing the ionic conductance of the various species
at any point during the course of titration.
The system under investigation showed a regular
rise in conductance upto the equivalence point, where
a sudden change in the slope occurs. This behaviour is
probably explained as follows: on addition of PT, PM
or SM acid, the ion-associates are formed by replacing
the drug cations (RNH+) by the highly mobile H+ ions,
so the conductivity increases. After the endpoint, more
acid reagent is added and the conductivity increases more
Ion-associate formation in conductimetric determination of some antihistamines
rapidly. A curve break is observed at a drug-reagent molar
ratio of 3:1 in case of all drugs with PT and PM acids,
while the ratio was 4:1 is for the case of SM acid. Figure
2 is a representative figure for conductimetric titration
of the cited drugs using PT acid to calculate the molar
ratio of the drug:reagent.
Effects of different water miscible solvents and tem-
perature on the endpoint position and the shape of the
titration curve were studied. Media of 5-20% ethyl and
isopropyl alcohols show no effect on the shape of the
titration curve and the position of the endpoint, while
acetone disrupts the shape of the curve and no endpoint
is observed. Temperatures up to 40°C do not affect the
shape or the endpoint position.
The reagent concentration in each titration must not
be less than ten times that of the drug solution in order
to minimize the dilution effect on the conductivity
throughout the titration. The optimum concentration of
the reagents is 10-2 M to achieve a constant and highly
stable reading within 1-2 min of mixing. Concentrations
less than this led to unstable readings and more time was
needed to obtain constant conductance values.
Determination of the active components in pure solu-
tions
Heteropolyacids react with quaternary ammonium
291
salts to form insoluble ion- associates. As a result, it may
be possible to use these reactions for quantitative deter-
minations of the nitrogen containing compounds in the
hydrochloride form. Because ion-associates formation
can be considered a phase transition between different
regimes of the system, these plots present, in general, a
linear behavior with different slopes at the beginning and
at the end of the volume axis. There is also a transition
(often very smooth) between the two regions for inter-
mediate values of the volume, and usually the endpoint
is determined by the intersection of two straight lines
in the conductivity-volume of reagent added plots. This
method is called the conventional or the normal method
for determination of the endpoint. However, this proce-
dure presents difficulties when the conductivity-volume
plot exhibits a weak curvature.
The behavior described above has suggested many
of the proposed approaches to obtain the endpoint,
these methods are based on the differentiation of the
conductivity data against the volume. Note that if the
conductivity-volume curve can be considered to show
linear regimes before and after the endpoint, as assumed
by the conventional procedure, the corresponding first
derivative plot behaves as a sigmoid, a curve that changes
smoothly from an asymptotic constant value to another
asymptotic constant value. The parameters of this curve
Figure 2. Conductimetric titration of 5.13, 4.14 and
2.94 mg (diluted upto 50 mL) of CTZ.Cl, HDZ.Cl and
DPH.Cl, respectively, using 10-2 M PT acid.
Canadian Journal of Analytical Sciences and Spectroscopy
292 Ahmed F. A. Youssef and Raafat A. Farghali
allow fitting not only of these two asymptotic values but
also the width of transition and its central point, which
should correspond to the endpoint. Nevertheless, this pro-
cedure presents several drawbacks. The main one is that
a numerical derivative, especially if the number of data
available is not very large, always introduces numerical
errors in the determination of the fitting parameters. In
addition, these errors join the inherent experimental
errors of the original conductivity versus volume data,
which are amplified in the numerical differentiation
procedure. Both types of errors lead to a sigmoidal-like
derivative, but with a noisy behavior instead of a perfect
and regular behavior. Thus, it seems preferable to obtain
an endpoint without any processing which would ulti-
mately introduce serious errors.
In the present work, a fitting method dealing with the
conductivity versus volume plots which allows direct
fitting of these data, was used to avoid any numerical
derivative. The equation used for this purpose, first de-
rivative f(x), can be described by using a Boltezmann
type sigmoid (31), which has the following analytical
expression:
where A1 and A2 represent the asymptotic value for small
and large values of x respectively, xo represents the end-
point and Δx deals with the width of transition.
Figure 3 shows a typical case for the determination
of HDZ.Cl and DPH.Cl by using 10-2 M SM and PM
acids, respectively, and applying the normal titration
curve, numerical first derivative (ΔC/ΔV) and the first
derivative f(x) methods. The results showed that in case
of f(x), curves with sharper endpoints were obtained.
The results of the pure drug determination, presented
in Table 1, showed that good recoveries and low relative
standard deviation values were obtained. The optimum
ranges for determination of CTZ.Cl, HDZ.Cl and DPH.
Cl are 5.13-30.78, 2.07-16.56 and 1.47-11.74 mg, in
the case of using of PT acid, 5.13-25.65, 2.07-16.56
and 1.47-11.74 mg, in the case of using of PM acid and
1.02-20.52, 2.07-16.56 and 2.93-11.74 mg in the case
of using SM, respectively, see Table 1. At such ranges,
sharp inflections (Figure 3) and stable conductance
reading were obtained. In order to establish whether the
proposed methods exhibit any fixed or proportional bias,
a simple linear regression of the observed drug concentra-
tion against the theoretical values was calculated using
Volume 51, No. 6, 2006
Kaleidagraph version 3.0, in which the slope, intercept,
and correlation coefficient values were found to be satis-
factory, see Table 2. Statistical evaluation of the regres-
sion lines showed that the standard deviation values of
the residual (Sy/x) are within the range of 1.19×10-2-11.0
× 10-2, while the standard deviation values of the slope
are within the range of 1.00 × 10-3 - 7.76 × 10-3. These
small figures point out the high precision of the proposed
method. Thus, it can be concluded that there are no sys-
tematic differences between the determined and the true
concentrations over the cited ranges.
The precision and accuracy of the proposed method
were assessed by calculating the student t-test (at 99.9%
confidence level) and F-test (at 95% confidence level)
(33) in comparison with the pharmacopoeial methods.
The calculated t-values range from 1.64 to 3.51 which
are lower than the tabulated value at 99% confidence
level and 4-degrees of freedom (4.60). Thus, there are
no systematic differences between the determined and
the true concentration over a wide range. The F-values
were found to be in the range 1.16-2.66 which are lower
than the tabulated value (6.39) at 95% confidence level
and 4-degrees of freedom. This means that there is no
significance difference between the proposed method
and the pharmacopoeial ones (5).
Determination of the active components in pharmaceuti-
cal preparations
In order to evaluate the applicability of the conducti-
metric method to pharmaceutical preparations, CTZ.Cl
and DPH.Cl were determined in Histazine-1 (syrup and
tablets) and Sultan (capsules), respectively, under the
same conditions as employed for the pure antihistamines.
The fact that the shapes of the conductimetric titration
curves of the pure antihistaminic and their correspond-
ing pharmaceuticals are nearly the same proves that the
excipients which might be present in the pharmaceutical
preparations do not affect the position of the endpoint.
The results obtained were in good agreement with the
labeled values for CTZ.Cl and DPH.Cl formulations,
see Table 3. Furthermore, the method was applied for
analyzing laboratory synthetic tablets containing HDZ.
Cl (10 mg), talc (50 mg), sucrose (70 mg), starch (40
mg), gelatin (60 mg), lactose (50 mg) and magnesium
stearate (60 mg). The percent recovery values were found
to be 98.37-99.72%, with standard deviation values from
0.12-0.29%.
For additional confirmation of the accuracy and preci-
sion of the proposed method, standard addition method
was performed by adding a known amount of pure drug
 Ion-associate formation in conductimetric determination of some antihistamines

Figure 3. Conductimetric titration of 8.28 mg HDZ.Cl with 10-2 M SM acid [A] and 8.80 mg DPH.Cl with 10-2 M PM acid [B] applying
the conventional procedure, the numerical first derivative plot (ΔC/ΔV) and Boltzmann sigmoid method f(x).
293

Canadian Journal of Analytical Sciences and Spectroscopy

294 Ahmed F. A. Youssef and Raafat A. Farghali

Table 1. Conductimetric determination of the hydrochlorides of cetirizine, hydroxyzine and diphenhydramine in pure solutions.
Taken PT PM SM
(mg) Found Recovery* RSD Found Recovery* RSD Found Recovery* RSD
(mg) % (mg) % (mg) %
Cetirizine hydrochloride
1.02 - - - - - - 1.01 99.02 1.70
2.56 - - - - - - 2.50 97.66 1.65
3.85 - - - - - - 3.80 98.70 1.60
5.13 5.04 98.25 0.99 5.10 99.42 1.13 5.15 100.39 1.01
10.26 10.37 101.07 1.02 10.25 99.90 1.20 10.27 100.10 1.19
15.39 15.60 101.36 0.98 15.40 100.06 1.19 15.50 100.71 1.10
20.52 20.70 100.88 1.10 20.58 100.29 0.98 20.54 100.10 1.25
25.65 25.80 100.58 1.05 25.64 99.96 1.01 - - -
30.78 30.98 100.65 0.95 - - - - - -
Hydroxyzine hydrochloride
2.07 2.13 102.90 1.54 2.10 101.45 1.22 2.10 101.45 1.20
4.14 4.19 101.21 1.33 4.16 100.48 1.15 4.13 99.76 1.59
8.28 8.30 100.24 1.45 8.27 99.88 1.01 8.30 100.24 1.20
12.42 12.45 100.24 1.38 12.41 99.92 1.10 12.37 99.60 1.23
16.56 16.60 100.24 1.21 16.53 99.82 1.13 16.62 100.36 1.01
Diphenhydramine hydrochloride
1.47 1.44 97.96 1.99 1.46 99.32 1.11 - - -
2.93 2.92 99.66 0.88 2.90 98.98 1.13 2.91 99.32 1.00
5.87 5.92 100.85 1.97 5.82 99.15 1.01 5.88 100.17 0.99
8.80 8.88 100.91 1.82 8.78 99.77 0.99 8.81 100.11 1.05
11.74 11.70 99.66 1.62 11.73 99.91 0.91 11.75 100.09 1.10
-: Out of the concentration application range
*: Mean value of five determinations

Volume 51, No. 6, 2006

 Table 2. Linear regression, F and t-test values obtained from determination of the investigated drugs in pure solutions using PT, PM and
SM.
Ion-associ- a Sy/x Sa b r F-value t-value
ates (6.39)1 (4.60)2
CTZ-PT 1.008 11.0 × 10-2 7.76 × 10-3 -2.7 × 10-2 0.999 2.19 1.99
CTZ-PM 1.002 1.88 × 10-2 1.16 × 10-3 -2.9 × 10-2 0.999 1.95 2.12
CTZ-SM 1.005 4.03 × 10-2 2.25 × 10-3 -3.7 × 10-2 0.999 2.13 1.85
HDZ-PT 0.998 4.79 × 10-2 4.04 × 10-3 5.3 × 10-2 1.000 1.88 1.36
HDZ-PM 1.008 2.73 × 10-2 2.31 × 10-3 3.4 × 10-2 1.000 1.98 0.99
HDZ-SM 0.996 1.19 × 10-2 1.00 × 10-3 2.3 × 10-2 0.999 1.25 1.01
DPH-PT 1.001 1.56 × 10-2 1.86 × 10-3 -2.8 × 10-2 0.999 2.01 1.96
DPH-PM 1.002 2.86 × 10-2 3.44 × 10-3 -2.8 × 10-2 0.999 1.19 0.88
DPH-SM 1.001 1.46 × 10-2 2.22 × 10-3 -2.0 × 10-2 1.000 1.27 1.05
a: Slope of the regression line of mg taken versus mg found; Sa: standard deviation of the slope; b: Intercept of the regression line; r: cor-
relation coefficient; 1: tabulated F-value at 95% confidence level and 4-degrees of freedom; 2: tabulated t-value at 99% confidence level and
4-degrees of freedom

Table 3. Conductimetric determination of CTZ.Cl, HDZ.Cl and DPH.Cl in their pharmaceutical formulations applying the proposed method and the standard addition method in
comparison with the pharmacopoeial methods (5).
Formulation Taken (mg) Proposed method (Recovery* % ± SD) Pharma- Standard addition method (Recovery* % ± SD)
name PT PM SM copoeial Added (mg) PT PM SM
method
(Recovery*
% ± SD)
Histazine-1 tablets (10 mg CTZ.Cl/tablet)
6.00 99.50 ± 0.23 98.83 ± 0.28 99.00 ± 0.19 98.50 ± 0.37 6.00 99.89 ± 0.11 99.53 ± 0.13 99.66 ± 0.16
10.00 99.78 ± 0.14 99.11 ± 0.22 99.06 ± 0.26 10.00 99.99 ± 0.09 99.54 ± 0.18 99.45 ± 0.10
Ion-associate formation in conductimetric determination of some antihistamines

Histazine-1 Syrup (1 mg CTZ.Cl/mL)

3.00 99.75 ± 0.19 99.52 ± 0.20 98.90 ± 0.15 98.99 ± 0.22 3.00 99.62 ± 0.10 99.45 ± 0.09 99.53 ± 0.09
6.00 99.47 ± 0.11 99.43 ± 0.19 99.10 ± 0.20 6.00 99.77 ± 0.07 99.32 ± 0.08 99.39 ± 0.1
Synthetic Tablets (10 mg HDZ.Cl/tablet)
2.50 99.72 ± 0.15 98.37 ± 0.18 98.98 ± 0.23 99.69 ± 0.19 2.50 99.80 ± 0.11 99.13 ± 0.10 99.47 ± 0.16
5.00 99.61 ± 0.12 99.09 ± 0.29 99.00 ± 0.19 5.00 99.77 ± 0.09 99.37 ± 0.16 99.230 ± 0.11
Sultan Capsules (50 mg DPH.Cl/capsule)
3.00 99.80 ± 0.10 99.51 ± 0.13 99.11 ± 0.17 99.90 ± 0.28 3.00 99.77 ± 0.16 99.69 ± 0.10 99.39 ± 0.19
5.00 99.90 ± 0.09 99.16 ± 0.18 99.26 ± 0.12 5.00 99.92 ± 0.13 99.53 ± 0.17 99.46 ± 0.14
*: Mean value of three determinations
295

Canadian Journal of Analytical Sciences and Spectroscopy

296 Ahmed F. A. Youssef and Raafat A. Farghali
to the pre-analyzed dosage forms. The results are sum-
marized in table 3 and considered to be satisfactory.
Conclusions
The proposed conductimetric method is suitable for
analysis of the three antihistaminic drugs in commercial
dosage forms. The SM method is the most sensitive
method for determination of cetirizine hydrochloride, PM
and PT methods are of equal sensitivity in the determina-
tion of diphenhydramine hydrochloride while the three
reagents are of equal sensitivity for determination of
hydroxyzine hydrochloride. Treatment of the conductiv-
ity-volume data with Boltezmann sigmoid method, for
determination of the endpoint, showed more accurate and
sharper endpoint in comparison with the normal titration
curve or the first derivative method, (ΔC/ΔV).
Generally, the present method was found to be simple,
inexpensive, sensitive and accurate, so this method is
useful and convenient for quality control and routine
determination of drugs in pure and pharmaceutical dos-
age forms.
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