Photodegradation and photostability-indication of mequitazine

Article abstract of DOI:10.1016/j.saa.2009.08.006

The photochemical behavior is investigated for mequitazine (MQ) illustrating possible mechanisms and photodegradation products formed. Accelerated photolysis is done for MQ under justified stress conditions by subjecting aqueous drug solutions to radiatio

Full text of DOI:10.1016/j.saa.2009.08.006

Spectrochimica Acta Part A 74 (2009) 740–745
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Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Photodegradation and photostability-indication of mequitazine
Ezzat M. Abdel-Moety∗, Mohamed A. Ibrahim, Mamdouh R. Rezk
Analytical Chemistry Department, Faculty of Pharmacy-Cairo University, Kasr El-Aini St, ET-11562, Cairo, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
The photochemical behavior is investigated for mequitazine (MQ) illustrating possible mechanisms and
photodegradation products formed. Accelerated photolysis is done for MQ under justified stress con-
ditions by subjecting aqueous drug solutions to radiation for specified period of time. Synthesis of the
main photodegradants, the sulfoxide, is achieved. Selective quantification of MQ, singly in bulk form,
pharmaceutical formulations and/or in the presence of its photodegradants is demonstrated.
The indication of stability has been undertaken under conditions likely to be expected at normal storage
conditions using a simple colorimetric method based on oxidation of the intact phenothiazine drug by
potassium iodate in acid medium to form a red colored product adequate for quantitative estimation of
the studied drug.
Received 5 January 2009
Received in revised form 5 July 2009
Accepted 5 August 2009
Keywords:
Colorimetry
Mequitazine
Photodegradation
Stability
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
In modern analytical laboratory, there is always a need for sig-
nificant stability-indicating methods of analysis. The present work
Phenothiazines exert photosensitization, where, their pho-
todecay may occur either by a free-radical chain process, i.e.
autooxidation, and/or by involving excited singlet molecular
oxygen, i.e. oxygenation [1,2]. Formation of the corresponding
sulfoxide was reported to be the primary decay product [3]. A
number of other photodecomposition products including N-oxides,
hydroxyl derivatives, dimeric or polymeric products, excited
monomers (excimers), in addition to sulfones, of various phe-
nothiazines were isolated and characterized [4–6]. The molecular
characteristics–phototoxicity relationship demonstrated that the
tricyclic moiety is essential for the phototoxic activities.
Mequitazine (MQ) is 10-(1-Azabicyclo[2.2.2]oct-3-yl-methyl)-
10H-pheno-thiazine (Fig. 1). It is an antihistaminic phenothiazine
drug prescribed for treating allergic rhinitis and urticaria [7].
MQ was determined by a number of spectrophotometric and
spectrofluorometric methods [8–10]. Assay of MQ was done
based on complex formation with palladium in the presence of
methylcellulose [11]. Chemiluminescence of MQ, utilizing single
photoelectron counting apparatus was carried out [12]. Determina-
tion of MQ by GC/MS [13–16] and by HPLC methods was described
[17–19].
aimed to study the photodegradation of MQ and to develop a sim-
ple colorimetric method for its quantification in pure form or even
in the presence of its photolytic degradants in bulk powder as well
as in pharmaceutical preparations.
2. Experimental
2.1. Instruments
o High-pressure mercury lamp, Hanau, (Germany), 12.5 W
short/long wavelengths (254 nm and 365 nm) equipped with a
quartz glass cooling mantle.
o Xenon lamp for suntest, Vilber Laurmat, providing UV–vis light
in the range of 300–800 nm, equipped with a quartz glass cooling
mantle.
o Spectrophotometer: Shimadzu UV-1601 PC, dual-beam UV–vis
spectrophotometer (Japan), with matched 1-cm quartz cells,
connected to an IBM-compatible PC. Bundled, UV-PC personal
spectroscopy software version 3.7 was used to process the
absorption spectra. The spectral band width was 2 nm with
wavelength-scanning speed of 2800 nm min−1
.
A possible photochemical process leading to photosensitivity
due to MQ was studied in comparison with that of chlorpromazine
[20] while the phototoxic potential of MQ was determined by the
photosensitizing action on microbial systems [21].
o IR spectrophotometer: Mattson Genesis II FTIRTM (USA), sam-
pling was undertaken as potassium bromide discs.
o Precoated TLC-plates, silica gel 60 F254 (20 cm × 20 cm, 0.25 mm),
E. Merck, (Germany).
o Gas chromatograph coupled to a mass spectrophotometer:
GC–MS-QB 1000 EX, Finnigan nat (USA).
o pH-meter, Digital pH/MV/TEMP/ATC meter, Jenco Model-5005
(USA).
∗
Corresponding author. Fax: +20 226173262.
E-mail address: eamoety@hotmail.com (E.M. Abdel-Moety).
1386-1425/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2009.08.006

E.M. Abdel-Moety et al. / Spectrochimica Acta Part A 74 (2009) 740–745
741
angle (∼60◦) to the surface of the solution. The distance from the
surface of the solution to the UV-lamp was ∼30 cm. The tempera-
ture was controlled to be 35 oC using cooling mantle. Continuous
mixing was done without interrupting the irradiation using long
glass rod, just to minimize the local thermal effect. Irradiation was
carried out for different time intervals (up to 180 min). At different
specified time intervals, a sample (5-mL) was withdrawn from the
vessel using a graduated pipette after short pre-stirring. Each taken
sample was placed into a test tube protected from light by careful
wrapping with aluminum foil. Protection measurement should be
pre-taken to avoid any possible long exposure of eyes and skin to
direct UV-irradiation. A part of the solution was protected from the
light source and was considered as a blank. Long-period irradia-
tion was interrupted by short dark phases to save the lamp-life.
The irradiated drug solution was fractionated by TLC on silica gel
60 F254 plates using n-butanol + water + 25% (w/v) aqueous ammo-
nia (17:2.8:0.2, by volume) as a developing solvent. The ultraviolet
spectrum was monitored for the withdrawn samples during irra-
diation.
Fig. 1. Structural formula of mequitazine.
o Graffin melting point apparatus model SMP1, Stuarts Scientific
Co. Ltd. (UK).
2.2. Materials and reagents
2.2.1. Materials
Reference MQ standard was kindly supplied by Rhone-Poulanc-
Rorer (France). Its potency was found to be 99.70 0.39% (n = 6),
according to a reference spectroscopic method [22].
2.3.2. Suntest on MQ
The dry powder of MQ was placed in pyrex vial, where, it was
subjected to direct irradiation using xenon lamp that provides
UV–vis light in the range 300–800 nm (having the same spec-
tral distribution of sunlight). The irradiance level is adjusted at
510 W h m−2. A dose of 45.7 W h m−2 could be permitted in the
UV (300–400 nm) and 112.5 k lx in the visible range (400–800 nm).
Accordingly, the samples were exposed to light for 15 h provid-
ing an overall illumination of 200 W h m−2 (near-UV energy) and
1.2 million lx h (visible energy), according to ICH guidelines.
The protected samples, wrapped with aluminum foil and placed
alongside the authentic samples, were considered as the dark con-
trols. To minimize the thermal effect, possibly caused by the xenon
lamp, the temperature was adjusted at the minimum value (35 ◦C)
and the lamp was switched off for 10 min per an illumination hour.
The treated drug powder after running the suntest was frac-
tionated by TLC on silica gel 60 F254 plates using the previously
described developing solvent. The ultraviolet spectral monitoring
was performed on the treated powder after running the suntest.
2.2.2. Pharmaceutical formulations
Primalan® tablets (5-mg per tablet) and Primalan® syrup
(0.5 mg mL−1) were kindly supplied by Amriya for Pharmaceutical
Industries (Egypt).
Pure drug, utilized without further treatments, and pharmaceu-
tical formulations were kept always protected from light.
2.2.3. Standard solutions
o Mequitazine hydrochloride (MQ·HCl) standard solution
(1 mg mL−1, as free base) was prepared by adding 3.1 mL of
0.1N HCl to 100 mg of MQ free base, dispersed in 70 mL distilled
water, in 100-mL volumetric flask. Shaking was done till com-
plete dissolution then the volume was completed with distilled
water.
o Photodegraded MQ·HCl working solution (1 mg mL−1, as free
base) was prepared by complete photolysis of the correspond-
ing solution by the aid of stress ultraviolet illumination in a
UV-cabinet. Complete photolysis was achieved after 24 h, as
shown by TLC-fractionation. The aqueous degraded solution was
evaporated under vacuum in a N2-atmosphere till dryness and
quantitatively transferred with distilled water into 100-mL flask.
The volume was completed with distilled water.
2.3.3. Synthesis of MQ sulfoxide
The preparation of pure phenothiazine sulfoxide was possible
by aqueous nitrous acid oxidation of the drug at room temperature
[23]. Accurate mass (1 × 10−2 M) of MQ (3.22 g) was suspended in
250 mL of distilled water, in a flask. Then ∼50 drops of HCl were
added with magnetic stirring. Excess of aqueous sodium nitrite
solution (120 drops, 0.1 g mL−1) was carefully added. Nitrogen was
bubbled through the solution for ∼2 h to remove the resulted nitro-
gen oxide gas. The reaction product was extracted twice with
chloroform to remove any foreign materials. Chloroform was dis-
carded and conc. ammonia solution (100 drops) was added to reach
pH 10 and allow sulfoxide separation. The liberated base sulfoxide
was extracted with chloroform and washed with water. The chloro-
formic extract was evaporated to dryness under nitrogen gas and
the residue was crystallized by cooling the solution overnight in
a refrigerator (∼5 ◦C). The product was purified using preparative
TLC, where the synthesized sulfoxide was characterized by deter-
mination of its m.p., TLC-fractionation, UV, IR spectrometry and
GC/MS.
All calculations and samples preparation for reference material
and pharmaceutical formulation were done on MQ free base. Solu-
tions were always freshly prepared on the day of analysis and stored
in a refrigerator, protected from light, to be used within 24 h.
2.2.4. Reagents
o Hydrochloric acid, chloroform, aqueous ammonia solution (25%,
w/v) and n-butanol: ADWIC, El-Nasr Pharm. Co. (Egypt).
o Potassium iodate: E. Merck (Germany).
o De-ionized water: bi-distilled from “Aquatron” Automatic Water
Still A4000, Bibby Sterillin Ltd. (UK).
2.3. Procedures
2.3.4. Colorimetric determination of MQ using potassium iodate
Aliquots equivalent to (0.5–4 mL) of MQ·HCl standard solution
(1 mg mL−1, as free base) were separately transferred to 100-mL
volumetric flask. For each flask 5 mL of aqueous potassium iodate
solution (0.1%, w/v) was added and then the volume was completed
with 0.05N HCl. The absorption spectrum of the color developed
2.3.1. Accelerated photolysis of an aqueous solution of the drug
Safety measures should be taken to avoid exposure of eyes
and skin to direct UV-irradiation. Solutions of MQ·HCl in water
(1 mg mL−1, free base) were irradiated by exposure to UV light
(254 nm) in an open container (12 cm Ø, 2 cm height) at a small

742
E.M. Abdel-Moety et al. / Spectrochimica Acta Part A 74 (2009) 740–745
was recorded at 513 nm against the corresponding reagent blank
after 6 min. Effect of potassium iodate concentration, acid concen-
tration and temperature were studied. The regression equation was
then computed and used for determination of unknown samples
containing MQ.
2.3.5. Assay of laboratory prepared mixtures containing different
ratios of MQ and its photodegradants using the proposed method
Aliquots of intact drug were mixed with portions of photode-
graded drug (as prepared in Section 2.2.3) to prepare different
mixtures containing 10–90% (w/w) degradation products, and pro-
ceed as mentioned under the described method. Calculate the
concentration from the computed regression equation.
Fig. 2. Absorption spectra of MQ·HCl (10 ␮g mL−1) irradiated for different time
2.3.6. Assay of pharmaceutical formulations
intervals (0–180 min).
o Primalan® tablets
At least twenty tablets were weighed to determine the average
weight per tablet. The tablets were powdered well and homoge-
neously mixed. A mass of powdered tablets equivalent to 50 mg of
MQ is transferred into a 100-mL flask. Extraction with 2 × 30 mL
of 0.05N HCl was done by vigorous shaking for ∼10 min, the
volume was completed with the same solvent. The well-mixed
extract was filtered through Whatman filter paper (No. 42). The
solutions were diluted to the same concentrations of the stan-
dard stock solution and analyzed as mentioned by the proposed
method.
irradiated phenothiazines degrade via a semiquinone free-radical
intermediate. Disproportionation of these free radical results in the
formation of the phenothiazine sulfoxide as indicated in Scheme 1
that shows the mechanism illustrating the formation of the phe-
nothiazine sulfoxide from the parent phenothiazine compound
during the ultraviolet irradiation.
As shown in Fig. 2, peaks characteristic for intact drug appear at
253 nm and 302 nm. During irradiation, the peak at 253 nm exhib-
ited a hypochromic shift and then disappeared after irradiation for
about 180 min. On the other hand, formation of new peaks was
observed at 232 nm, 271 nm, 198 nm and 342 nm, which are the
characteristic maxima of the corresponding sulfoxide.
o Primalan® syrup
Portions of the syrup solution were diluted with 0.05N HCl and
completed as mentioned under the proposed method (in Section
2.3.4).
3.1.2. TLC-fractionation
Working standard solution of MQ·HCl (1 mg mL−1, free base)
after irradiation time of 180 min was evaporated to dryness under
reduced pressure in rotavapor, in an atmosphere of nitrogen
gas. The obtained residue was dissolved in the least amount
of distilled water. Fractionation of the components of the drug
degradation was done on thin layers of silica gel F254 using n-
butanol + water + 25% (w/v) aqueous ammonia solution (17:2.8:0.2,
by volume) as the developing solvent. The developed plate was
visualized under short UV-lamp and/or by subjecting it to iodine
vapors. TLC-fractionation of photodegraded MQ·HCl (irradiated
for 3 h) showed seven photodegradates (with Rf-values 0.05–0.2)
separated from the intact drug (its Rf-value = 0.26). Like other phe-
nothiazines, MQ undergo a series of molecular breakdown. Some of
the less stable primary photolytic products may be easily converted
to different stable secondary photodegradants on longer exposure
to light. Early investigations on phenothiazines’ photoxidation indi-
cated the formation of the corresponding sulfoxides as the major
products [5].
3. Results and discussion
3.1. Accelerated photolysis of an aqueous solution of MQ
The aim of the work was to investigate the photodegradation
possibly occurring as a result of the UV-irradiation of aqueous solu-
tions of the selected phenothiazine drug.
3.1.1. Spectral changes
Accelerated drug photolysis was carried out for MQ by irradiat-
ing its aqueous solution (1 mg mL−1, free base), utilizing a 12.5-W
UV-lamp (254 nm) at a specified distance and angle in an open
container. The color of irradiated MQ solution changed gradually
from colorless to faint pink and finally reddish-brown by the end
of irradiation period. The spectral monitoring revealed an increase
in the light absorption at ∼513 nm inducing the red coloration. The
intensity of the formed color was time-dependent; the more the
exposure, the more intense was the color. Generally, the princi-
pal photodegradation products of the phenothiazines are reported
to be the corresponding sulfoxides, as the major photodegradates.
Felmeister and Disher [5] studied the photodegradation of chlor-
3.1.3. pH profiling
The change in the pH-value was determined during different
time intervals of UV-irradiation for MQ·HCl. A significant increase
in hydrogen ion concentration, i.e. decrease in the pH-value, on irra-
diation was noticed. It can be explained on the basis of the reaction
of the short-lived phenazathionium ion with water to yield the S-
oxide (Scheme 1). Two hydrogen ions result for each molecule of the
S-oxide formed. Thus, on irradiation of MQ·HCl solution pH-value
decreased from 3.1 to 2.8.
promazine (CPZ) and the production of a stable red radical, CPZ•
+
upon UV-irradiation. The observed red color in the case of MQ may
be attributed to a similar stable red radical. Such radicals decom-
pose on heating; so upon heating the colored drug solution, color
fainting then total discharging was observed.
The distribution of electrons in the MQ molecule, like other phe-
nothiazines, may lead to the formation of many radical forms, such
as at S-atom, at N10-atom and between S- and N-atoms in the phe-
nothiazinering, as aresultofpossibleresonances [1]. Thepossibility
of formation of MQ radical at the S-atom is expected under the
influence of short lasting UV-irradiation.
3.1.4. The kinetic order
Estimation of the kinetic order of the photodegradation of
MQ·HCl solution could be done by calculating the percentage of the
remaining drug concentration (Ct/Ci) %, and its logarithmic value at
different time intervals during the irradiation, where Ct (is the con-
Fig. 2 shows the ultraviolet absorption spectra resulting upon
irradiation of MQ·HCl at different time intervals. The ultraviolet

E.M. Abdel-Moety et al. / Spectrochimica Acta Part A 74 (2009) 740–745
743
Scheme 1. Possible reaction mechanism for the oxidation of mequitazine by potassium iodate.
centration at time t) and Ci is the initial concentration. Assay of
3.2. Suntesting on MQ
MQ was carried out by adopting the developed potassium iodate
colorimetric method. Plotting the percentage of the remaining drug
concentration (Ct/Ci) %, versus time showed curved correlation indi-
cating the complicity of the photolysis process. Some of the less
stable primary photolytic products may be easily converted to
different stable secondary degradation compounds on longer expo-
sure to light. The photodegradation process of MQ·HCl followed
first order kinetics during early stages of photodegradation as indi-
cated by the straight line relationship between log the % of the
remaining drug concentration versus time, the linear correlation
extends from the beginning of the irradiation process till 60 min,
i.e. at the early illumination periods, then linearity is deformed,
shown in Fig. 3).
Suntesting for MQ was carried out to study its photostability in
the solid form and compare it with the photostability of the solution
form.
Pure powder of MQ free base was subjected in heat resistant
pyrex vials to the Xenon lamp. After subjecting the dry MQ pow-
der to the irradiation dose (for 15 h), the vials were then opened
and the contents were examined. Irradiated MQ powder was still
white in color but with melting point of 150 ◦C, instead of 130 ◦C
for the non-irradiated drug. The ultraviolet spectra, shown in Fig. 4
show quite difference from the corresponding spectrum of the orig-
inal non-irradiated pure MQ. Such findings indicate that a possible
decomposition could be occurred.
TLC-fractionation of the photolyzed samples was applied,
where, only few photodegradates (including the sulfoxide) were
observed. MQ showed certain stability when present in the solid
form more than that if it was in solution but still photo-labile in
both cases.
3.3. Synthesis of MQ sulfoxide
Sulfoxidation resulting in 5-sulfoxide metabolite is a common
bio-transformation pathway for all phenothiazines and it is the
main photodegradate formed during ultraviolet irradiation [24].
MQ sulfoxide could be obtained synthetically by nitrous acid
oxidation. It is yellowish-orange crystalline powder (melting range
of 214–218 ◦C). The synthesized sulfoxide is bitter in taste and
freely soluble in dilute acids and in methanol, but practically insol-
uble in water. TLC-fractionation shows the MQ sulfoxide with
retention value of 0.1, using the specified conditions mentioned
Fig. 3. Plotting of log the % remaining (Ct/Ci) % of photolyzed solution (1 mg mL−1
of MQ·HCl.
)

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E.M. Abdel-Moety et al. / Spectrochimica Acta Part A 74 (2009) 740–745
Fig. 6. Spectrum of the reaction product obtained from the reaction between
30 ␮g mL−1 mequitazine and potassium iodate.
Fig. 4. Absorption spectra of pure (––) and suntest irradiated (. . .. . .) mequitazine
(10 ␮g mL−1).
before. The scanned spectrum of MQ sulfoxide demonstrates the
characteristic maxima of the sulfoxide at 232 nm, 271 nm, 298 nm
and 342 nm (Fig. 5). The prepared sulfoxide was characterized by
IR spectroscopy showing a peak at 1020 cm−1 corresponding to
sulfoxide stretching which is absent in the spectrum of pure MQ.
GC/MS-spectrum shows a peak at m/z 338 corresponding to molec-
ular ion of MQ sulfoxide with a molecular formula of C20H22N2SO.
acid, oxidizing agent and concentration of the phenothiazine drug.
When a large excess of oxidizing agent was added the red color was
quickly destroyed leaving colorless sulfoxide (Scheme 1).
Only intact MQ is oxidized in the proposed method by potassium
iodate in acid medium. The isolated photodegradates of MQ and
the chemically prepared sulfoxide derivative fail to produce the
red color obtained by adopting the proposed colorimetric method.
It could be considered therefore, stability-indicating method for
estimating MQ in the presence of its photodegradants weather in
solution or solid forms.
3.4. Colorimetric determination of MQ using potassium iodate
Different colorimetric methods have been reported for the
determination of phenothiazines. The general method of Cavatorta
[25] to quantitate unoxidized phenothiazine derivatives by color
complex formation with palladium chloride has been reported.
Phenothiazines react with ceric ammonium sulfate, first by form-
ing a red colored semiquinone free radical followed by colorless
sulfoxide derivative [26].
Ellaithy et al. [27] observed that chlorpromazine, promethazine
and fluphenazine hydrochlorides undergo one-electron oxidation
with potassium iodate in acid medium to a red intermediate which
is believed to be a free radical with a semiquinoid structure. The
stability of the red color obtained depends on the concentration of
The red color produced from the reaction between MQ and
potassium iodate shows absorption maxima at 513 nm, as shown
in Fig. 6. Optimization of the reaction conditions was done and it
was found that maximum color intensity was attained after 6 min at
room temperature using 5 mL of aqueous potassium iodate solution
of concentration of 0.1% (w/v) and the obtained color remains sta-
ble for few minutes. Maximum color intensity was attained when
using 0.05N HCl and temperature between 10 and 30 ◦C i.e. room
temperature. The studied range for potassium iodate solution con-
centration was 0.05–0.5% (w/v), while the studied range for the
acid concentration was 0.02–0.5N HCl. The temperature effect was
investigated in the range of 10–70 ◦C.
A linear relationship was obtained in the range of 5–40 ␮g mL−1
of MQ. The regression equation was computed and found to be:
A = 0.02138C + 0.0378 (r = 0.999)
where A: absorbance at 513 nm, C: concentration of MQ (␮g mL−1),
and r: the correlation coefficient.
The precision of the proposed method was confirmed by the
analysis of different concentrations of pure samples. The mean per-
centage recovery was found to be 100.12 0.679.
3.5. Stability-indication
To assess the stability-indicating efficiency of the proposed
method, the photodegraded MQ was mixed with the pure drug
at different ratios and the mixtures were analyzed by the pro-
posed method. Satisfactory selectivity could be confirmed in
the determination of MQ even in the presence of up to ∼70%
(w/w) of its photodegradants by adopting the described colori-
metric method. The mean percentage recovery was found to be
100.06 0.724.
Fig. 5. Spectra of mequitazine (––) and its sulfoxide (—-) each 10 ␮g mL−1
.

E.M. Abdel-Moety et al. / Spectrochimica Acta Part A 74 (2009) 740–745
745
Table 1
ence method [22]. The calculated t- and F-values [28] were found
to be less than the corresponding theoretical ones, confirming good
accuracy and excellent precision (Table 2). Assay parameters and
method validation are declared in Table 3.
Determination of mequitazine in its pharmaceutical for-
mulations by the proposed potassium iodate method.
Preparation
Mean SD
CV
Primalan® tablets
BN: 406704
100.06 0.675
0.675
100.23 0.469
0.468
4. Conclusion
Primalan® syrup
BN: 552302
Unlike the mostly recommended HPLC-procedures, the pro-
posed colorimetric method is simple and not expensive. The
reagents used in the proposed method are cheap and readily avail-
able. The procedures applied do not involve any critical reactions
or tedious sample preparations. This aspect of spectrophotomet-
ric analysis is of major interest in analytical pharmacy since it
offers distinct possibility of assaying MQ in its pharmaceutical
formulations without interference due to the excipient or the pho-
todegradation products.
The suggested method is found to be simple, accurate, selec-
tive and stability-indicative one unlike the reference spectroscopic
method [22]. It could be applied for routine analysis of pure drug
or in its pharmaceutical formulations.
Table 2
Statistical comparison for the results obtained by the proposed potassium iodate
colorimetric method and the reference method for the analysis of mequitazine.
Parameter
The proposed method
The reference
method [22]
Mean
SD
CV
n
Variance
Student’s t-test
F
100.12
0.679
0.678
99.70
0.396
0.397
6
8
0.461
0.157
1.511 (2.179)*
2.94 (4.88)*
*
Figures in parentheses are the theoretical t- and F-values at P = 0.05 [28].
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[24] S.G. Dahl, in: E. Usdin, S.G. Dahl, L.F. Gram, O. Lingjerde (Eds.), Clinical Phar-
macology in Psychiatry: Neuroleptic and Antidepressant Research, MacMillan,
London, 1981, p. 125.
Table 3
Assay parameters and method validation for the reaction of
mequitazine with potassium iodate.
Parameter
Mequitazine
ꢀmax
513 nm
5–40
Linearity range (␮g mL−1
)
LOD (␮g mL−1
LOQ (␮g mL−1
)
)
1.31
3.96
A1%
213.84
6895.69
0.0214
0.0378
100.12
0.679
0.678
0.999
1cm
-
C(apparent molar absorpitivity)
Slope
Intercept
X
SD
CV
r
RSD (%)a
RSD (%)b
0.485–0.515
0.441–0.497
aThe interday (n = 6) and bthe intraday (n = 5) relative standard devi-
ations of samples of concentrations (20 ␮g mL−1 and 40 ␮g mL−1) for
mequitazine.
3.6. Application of the proposed methods to the pharmaceutical
formulations
The suggested method was successfully applied for the deter-
mination of MQ in Primalan® tablets and syrup, showing good
percentage recoveries. The validity of the suggested methods was
further assessed by applying the standard addition technique
(Table 1) and the precision was also expressed in terms of relative
standard deviation of the inter-day and intra-day analysis results.
[25] L. Cavatorta, J. Pharm. Pharmacol. 11 (1959) 49.
[26] T.N. Tozer, L.D. Tuck, J. Pharm. Sci. 54 (1965) 1169.
[27] M.M. Ellaithy, M.G. El-Bardicy, M.W. Ibrahim, A.K.S. Ahmad, J. Pharm. Belg. 38
(1983) 309.
3.7. Statistical analysis
[28] M.R. Spiegel, L.J. Stephens, L.F. Gram (Eds.), Schaum’ Outline of Theory and
Problems of Statistics, Schaum’ Outline Series, New York, 1999.
Results of the suggested method for determination of MQ were
statistically compared with those obtained by applying the refer-