172
PLASTIC BUMETANIDE MEMBRANE SENSOR AND ITS APPLICATIONS
IN PHARMACEUTICAL PREPARATIONS AND BIOLOGICAL FLUIDS
Maha El-Tohamy, Magda El-Maamly and Abdalla Shalaby*
‫تم تطوير إلكترود غشائي بالستيكي (مسرى كهربيي ديييي (ميا ميادل بيولي يلييا ك)ويرييي يرتكيي ن)يل ررييو رل تيررب‬
‫ل ادل تلجستو وسفات بيوميتانيي ك ادل نشطة كهربيا ً وذلك لتقيير مادل بيوميتانيي بشك)ه رللقي و ي رل ستحضررت رلصيييننية‬
‫ وكانت رل ادل رل )ينة هي دري بيوتيا سييباكات وديي غطيت رنسيتجابة رل طيية مييى تركييي ل)ييور‬،‫و ي رلسورئا رلبيولودية‬
‫ وديي تيم‬8-5 ‫نقيي وكيا مييى ررل رلهييييوديلي رل )يي هيو‬/‫ مي))يي ولت‬58.5 ‫ نييايي ب ييا مقييري‬10-3x1 – 10-6x1
‫ ومسيوغات رلييور ك يا تيم تطبييا رإللكتيرود رل قتير‬،‫ ورلق)ويييرت‬،‫رإلبالغ نا رلتييرالالت رللاتجية ميا رلكاتيونيات رلشيائ ة‬
‫لتقيير مادل بيوميتانيي بشك)ها رللقي وتجانس رل حتوى ي رردررص وكانت رللتائج متور قة دير ً مع رللتائج رلتيي تيم رلحصيو‬
NFXX ‫ رلرس ي وكتيب رلوصفات ررمريكي‬USPXXV ‫ن)يها باست يرم طريقة دستوي رردوية ررمريكي‬
A novel plastic poly (vinyl chloride) membrane electrode based on bumetanide-tungstophosphate
ion association as electroactive material for the determination of bumetanide in pure form,
pharmaceutical formulations and biological fluids is developed, in which the plasticizer is di-butyl
sebacate. The linear response covers the range of 1x10-6-1x10-3M drug concentration with a slope
of 58.5 mV/decade. The practical pH range is 5-8. Interferences from common cations, alkaloids
and drug excipients are reported. The proposed electrode has been successfully applied to
determine bumetanide in pure form and the content uniformity for tablets. The results are
correlated well with those obtained by the official USP 25, NF 20 method.
Key words: Bumetanide, bumetanide plastic membrane, pharmaceutical analysis, potentiometric
methods, pontent uniformity.
Introduction
Bumetanide [3- ( butyl amino) - 4- phenoxy - 5 sulfamoyl benzoic acid] is an important pharmaceutical compound classified as a strong diuretic
agent (loop diuretic). It is indicated for the treatment
of oedema associated with congestive heart failure,
hepatic and renal diseases, including the nephritic
syndrome (1).
The content of bumetanide tablets is usually only
1.0 mg, therefore, the analytical methods used for the
assay should be very sensitive. Several analytical
methods have been reported for the determination of
bumetanide in pure form, pharmaceutical formulations or in biological fluids including spectrophotometry (2,3), capillary zone electrophoresis (4), high
Analytical Chemistry Department, Faculty of Pharmacy, Zagazig
University, Zagazig Egypt
*
To whom correspondence should be addressed.
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
performance liquid chromatography (5-9), gas chromatography-mass spectrometry (10-12), fluorimetry
(13), liquid chromatography-mass spectrometry (14).
Bumetanide as a diuretic agent sometimes misused
by competitors for two main reasons, namely: To
reduce weight quickly in sports where weight
categories are involved. Also to reduce the
concentration of abused drugs by diluting the urine.
Health risks are involved in such misuse because of
serious side effects which might occur. Therefore,
due to the increasing importance of bumetanide and
its abused in sports a fast method for routine analysis
and quality control of commercial formulations is
very desirable. The aim of this work was to develop
a novel sensitive, fast and low cost for the routine
quality control (assay, content uniformity) and
dissolution study of bumetanide in pure form and in
pharmaceutical formulations.
PLASTIC BUMETANIDE MEMBRANE SENSOR
Experimental
Reagent and Materials:
All chemicals used of analytical or pharmacopoeial grade. Doubly distilled water was used
throughout the experiments. Bumetanide was provided by Memphis-Delagrange, (France), poly (vinyl
chloride) (PVC) was from Aldrich (Germany), dibutyl sebacate was from Fluka (Buchs, Switzerland),
tungstophosphoric acid and tetrahydrofuran (THF)
were from Memphis-Delagrange (France), (Burinex®
tablets, Edemex® tablets and ampoules) were
purchased form local drug stores. Stock bumetanide
solution (1x10-1M) was prepared daily by dissolving
an appropriate amount of the drug in double distilled
water. More dilute solutions were prepared by
appropriate dilution. All solutions were stored at
darkness in airtight containers.
Apparatus:
Jenway 3010 pH/mV meter (U.K.) with a bumetanide-PVC membrane electrode in conjunction
with double Junction Ag/AgCl electrode (Orion 9002) (Taiwan, R.O.C.) containing 10 % w/v
potassium nitrate in outer compartment. An Orion
91-02 glass-calomel combination electrode, (Taiwan,
R.O.C.) was used for pH adjustment. All potentiometric measurements were carried out at 25±1ºC
with constant magnetic stirring.
Recommended procedures:
Preparation of bumetanide ion-pair:
The ion-pair was prepared by mixing 50 ml
aliquots of 1x10-2 M bumetanide and tungstophosphoric acid. The resulting white precipitate was
filtered through G4 sintered glass crucible and
washed thoroughly with deionized water then dried
at room temperature for 24 hours.
Membrane composition:
The membrane was prepared by dissolving 190
mg of powdered PVC, 0.35 ml of the plasticized (dibutyl sebacate) and 10 mg of the ion-pair in 5 ml
tetrahydrofuran (THF). The solution was poured into
a petri dish (3 cm in diameter), covered with a filter
paper and the solvent was allowed to evaporate
slowly at room temperature.
Electrode Construction:
A punched circular membrane was attached to a
poly–ethylene tube (8 mm in diameter) in an electroSaudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
173
de configuration by means of PVC-THF solution. A
mixture containing equal volumes of 1x10-3 M bumetanide and potassium chloride was used as internal
reference solution in which the Ag/AgCl reference
electrode was dipped. The constructed electrode was
pre-conditioned after preparation by soaking for at
least 24 hours in 1x10-3 M drug solution and stored
in the same solution. The electrochemical system is
represented as follow: Ag/AgCl/inner solution/membrane/test solution/KCl salt bridge//SCE.
Electrode Calibration:
10 ml aliquots of 1x10-1-1x10-6 M standard
bumetanide solution were transferred into 50 ml
beaker and the sensor in conjunction with Ag/AgCl
reference electrode were immersed in the solution.
The measured potential was plotted against the
logarithm of drug concentration. The electrode was
washed with deionized water and dried with tissue
paper between measurements.
Effect of pH:
The effect of pH on the potential of the electrode
was measured using two pH/mV meters. The combined glass calomel electrode was connected to one
instrument and the PVC-bumetanide membrane with
the double junction Ag/AgCl reference electrode was
connected to the second instrument. Thirty ml
aliquots of 1x10-6 M, 1x10-5 M, 1x10-4 M, 1x10 -3 M,
drug solutions were transferred to a 100 ml beaker
where the three electrodes were immersed, the
potential readings corresponding to different pH
values were recorded. The pH was gradually
increased or decreased by the addition of small
aliquots of dilute solutions of 0.1 N sodium hydroxide or 0.1N hydrochloric acid respectively and the
pH-mV was measured and plotted.
6. Selectivity of the electrode:
Selectivity coefficients were determined by the
separate solution method (15) in which the following
equation was applied.
Pot.
1/z
log K bumet.Jz+=(E2–E1)/S + log [Bumet.]– log [Jz+].
Where E1 is the electrode potential in 1x10-3 M
bumetanide solution. E2 is the potential of the
electrode in 1x10-3 M solution of the interferent ion
Jz+ and S is the slope of the calibration plot. The
selectivity of the electrode towards sugars, amino
acids, certain cations and alkaloids was studied. In
some cases, when the selectivity coefficients were
174
not very high, both matched potential and mixed
solution methods (16) were used. The tested
interferents are listed in Table 2.
Standard addition method:
This technique is usually employed when the
sample matrix has an unknown but probably
significant effect on the cell potential. First, the cell
potential in the sample is recorded and then a volume
of a solution containing a known concentration of the
primary ion is added. This is commonly a small
volume of concentrated primary ion solution to
minimize dilution effects. The cell potential in this
altered sample is also recorded. The change in
response is related only to the change in primary ion,
and from the Nernst equation the difference in
electrode potential can be calculated. Therefore, an
electrode was immersed into a sample of 50 ml with
unknown concentration (ca. 10-4M) and the equilibrium potential of E1 was recorded. Then 0.1 ml of
10-1 M of bumetanide standard was added into the
testing solution and the equilibrium potential of E2
was obtained. From the change of Δ E (E2-E1) one
can determine the concentration of the testing sample
(17).
Analytical applications:
1. Determination of bumetanide in dosage forms:
1.1 Tablets
The content of ten tablets were shaken with 100
ml distilled water to obtain different concentrations
in the range of 1x10-3–1x10-6M. The prepared
solutions were adjusted to pH 5 using 0.1 N dilute
hydrochloric acid. The PVC bumetanide membrane
electrode was immersed in the solution. The
electrode system was allowed to equilibrate with
stirring and the e.m.f. recorded and compared with
the calibration graph. The standard addition (spiking
technique) was also applied by recording the
electrode potential after the addition of 0.1 ml of
standard 1x10-1M bumetanide solution to the above
drug test solutions.
1.2.Ampoules
The prepared ampoules solution was diluted with
deionised water to give serial dilutions ranging from
1x10-3-1x10-6M. These solutions were transferred
into 50 ml beaker, adjusted to pH 5 and the
procedure was completed as described under tablets.
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
EL-TOHAMY ET AL
1.3. Content uniformity assay of bumetanide tablets:
Ten individual tablets of 1.0 mg per tablet were
placed in separate 100 ml beaker and dissolved in
90-100 ml of distilled water. The electrode was
directly immersed into 10 ml of each sample for five
times and should be washed with deionized water to
reach steady potential between the individual
measurements. The mean potential was used to
evaluate the content uniformity from the calibration
graph. Fig. 4, showed content uniformity of
bumetanide in tablets.
1.4. Dissolution test
Place 900 ml of water into the dissolution vessel
and equilibrate to 37 + 0.5, place one tablet in the
dissolution vessel and immediately operate the
apparatus at 2:50 rpm after the stated time, withdrown 20 ml of the dissolution medium. For the
potentiometric determination, after an appropriate
time interval (0.5-3 min), the potential values were
recorded, and the amount of the bumetanide was
calculated from the calibration graph. In order to
investigate all the important physical processes
during the dissolution period, the released profile
was numerically simulated by a typical equation
(18). Fig. 5, showed the dissolution profile of
bumetanide 1.0 mg tablets.
2. Determination of bumetanide in biological fluids:
2.1. Preparation of urine samples:
Place 10 ml urine in 100 ml volumetric flask.
Add distilled water and adjust the pH to 5 using 0.1N
dilute hydrochloric acid. Known amount from stock
solution of bumetanide
1.0x10-1M was added to
form serial dilutions from 1x10-6 M to 1x10-3 M. The
potential response for the concentrations was
measured using bumetanide-tungstophosphate-PVC
membrane electrode, with constant magnetic stirring.
The calibration graph was plotted. The unknown
concentrations of the drug were calculated from the
calibration graph using standard addition method.
2.2. Preparation of serum samples:
Place 5 ml human serum in 25 ml volumetric
flask complete to volume using normal saline 0.9N
sodium chloride. The pH was adjusted to 5 using
0.1N dilute hydrochloric acid. The samples were
found free from bumetanide, so they were prepared
by spiking with known amounts of analyte, using
PLASTIC BUMETANIDE MEMBRANE SENSOR
175
1x10-1 M stock solution of bumetanide . The
calibration graph was plotted, then determination of
different samples was performed from adequate
aliquot by standard addition method.
COOH
I
O
II
H2N-S
II
O
Results and discussion
Table 1: Critical response characteristic of bumetanide-tungstophosphate-PVC membrane electrode.
Parameter
Value
decade)a
Slope (mV per
Intercept E (mV)b
Correlation coefficient, r.
Linear range (mole-1)
Lower limit of detection (mole-1)
Working pH range.
Response time for
1x10-4M bumetanide/sec.
Life time /day.
58.5±0.2
499.3
0.9999
1x10-3-1x10-6
4x10-7
5-8
30
45
a
Standard deviation of average slope values for multiple
calibration (n=6).
b
Standard deviation of values recorded over a period of 45 days
(n=6).
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
NH(CH 2 )3 -CH3
w12 PO40
Fig. 1. Bumetanide-tungstophosphate ion pair complex.
400
300
Electrode potential/mV
Nature and response characteristics of the
electrode bumetanide reacts with tungstophosphoric
acid to form a stable bumetanide-tugstophosphate
ion-pair complex ( Fig. 1), which is water insoluble
but readily soluble in an organic solvent such as
tetrahydrofuran. The complex was prepared and
tested as active material with di-butyl sebacate as a
solvent mediator in a poly (vinyl chloride) membrane response for bumetanide. The critical response
characteristics of bumetanide-PVC membrane electrode were determined and results are summarized in
Table 1. The electrode exhibits a Nernstain response
over the concentration range from 1x10-3–1x10-6M
bumetanide with a cationic slope of 58.5±0.2
mV/decade change in concentration (Fig. 2). The
choice of membrane solvent to achieve the required
selectivity is based on its electric permittivity and its
immiscibility with aqueous phase, high viscosity,
low solubility of the matrix in the membrane and
ability to dissolve ion-pair complex. The response
time of the electrode was tested for 1x10-3–1x10-6M
bumetanide solutions. The sequence of measurements was from low to high concentrations. This
electrode exhibits a fast dynamic response of about
30-40 seconds. The electrode used for a period of 45
days without significant change in the electrode
parameters.
I
O
I
+
200
100
0
1
2
3
4
5
6
7
- log conc. of bumetanide
Fig. 2: Typical calibration graph of bumetanidetungstophosphate-PVC membrane electrode.
Table 2: Selectivity coefficient for some sugars,
amino acids and common cations with bumetanidetungstophosphate-PVC membrane electrode.
Pot
Interfe- -log KBumet
rent
SSMa MSMb
+
Na
2.54
2.85
K+
2.39
2.42
NH+4
2.72
2.96
Mg2+
2.58
3.01
Ca2+
2.97
3.12
Sr2+
3.89
—
Co2+
4.12
—
Cu2+
3.97
—
Pb2+
4.58
—
Mn2+
4.01
—
Ni2+
2.60
2.98
Ba2+
2.65
2.87
Al3+
3.86
—
a
Separate solution method.
Pot
Interferent
-log KBumet
SSMa MSMb
Glucose
2.67
2.94
Lactose
2.73
2.92
Maltose
3.91
—
Dextrose
3.98
—
Quinidine
2.43
2.65
Atropine sulphate 2.55
2.74
Sulfathiazole
2.53
2.76
Urea
2.68
3.01
Tryptophan
2.61
2.95
Starch
3.67
—
Glycine
4.17
—
b
Mixed solution method.
176
EL-TOHAMY ET AL
Table 3: Determination of bumetanide in pure form
using bumetanide-tungstophosphate-PVC membrane
electrode in comparison with reference method (18).
100.5
Statistical Reference
Direct Potentiometry
Parameters method Calibration
Standard
(18)
graph
addition
method
Mean % recovery 99.74
99.62
99.67
N
6
7
6
Variance
0.220
0.144
0.121
S.D.
0.469
0.379
0.348
S.E.
0.191
0.143
0.142
R.S.D.
0.470
0.380
0.349
(0.503)(2.201)*
(0.294)(2.228)*
(1.53)(4.39)*
(1.82)(5.05)*
"t"
F
% of bumetanide content
100
99.5
99
98.5
98
97.5
97
10 9
8 7
6
5
4
3
2
1
Numbers of Bumetanide 1.0 mg Tablets
Fig. 4 . Content Uniformity of Bumetanide in Tablets.
* Theoretical values of ''t'' and F at P=0.05
200
180
160
140
NUMBER
120
4.00
3.00
100
2.00
80
1.00
3
4
5
6
7
8
9
PH
Fig. 3: The effect of pH on electrode potential/mV of
bumetanide-tungstophosphate-PVC membrane electrode.
1.0x10-3(1), 1.0x10-4(2), 1.0x10-5(3),1.0x10-6M(4).
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
1. Quantification, accuracy and precision:
Direct potentiometric determination of bumetanide using the bumetanide- tungstophosphate-PVC
membrane electrode was performed and calculated
from the calibration curve.
The statistical data of the analytical results
obtained by the proposed method (direct and
standard addition techniques) for the drug in pure
form are listed in Table 3. Furthermore, the results
obtained were encouraging so the proposed method
was applied for the determination of bumetanide in
some of its pharmaceutical preparations. In both
cases, the results obtained were compared with the
reference method (Dissolve about 1.00 g of
bumetanide accurately weighed in 150 ml of
methanol. In 250 ml conical flask, add phenol red
and titrate with 0.1 N NaOH. Perform a blank
determination and make any necessary correction
(18). The results were listed in Table 4.
PLASTIC BUMETANIDE MEMBRANE SENSOR
177
Table 4: Comparative analytical results of the proposed and official method for the tested drug in some
pharmaceutical preparations.
Sample and Source
Statistical
parameters
Mean % recovery
N
Variance
S.D.
S.E.
R.S.D.
t
F
Mean % recovery
N
Variance
S.D.
S.E.
R.S.D.
t
F
Mean % recovery
N
Variance
S.D.
S.E.
R.S.D.
t
F
Burinex® tablets
1mg/tablet
(Leo/Minapharm)
Edemex® tablets
1mg/tablet
(Memphis-Delagrange)
Edemex® ampoules
0.5mg/ml
(Memphis-Delagrange)
Direct potentiometry
Official method (18)
Calibration
Standard Addition
graphs
method
99.69
99.42
99.76
6
5
6
0.113
0.232
0.089
0.336
0.482
0.298
0.137
0.216
0.122
0.337
0.485
0.299
(0.382)(2.228)*
(1.371)(2.262)*
(1.27)(5.05)*
(2.61)(5.19)*
99.68
99.86
99.62
6
5
6
0.149
0.428
0.358
0.386
0.654
0.598
0.158
0.292
0.244
0.387
0.655
0.600
(0.206)(2.228)*
(0.631)(2.262)*
(2.40)(5.05)*
(1.20)(5.19)*
99.91
99.71
99.72
6
5
5
0.250
0.438
0.548
0.500
0.662
0.740
0.204
0.296
0.331
0.500
0.664
0.742
(0.489)(2.262)*
(0.023)(2.306)*
(2.19)(5.19)*
(1.25)(6.39)*
* All values of ''t'' and F are in P=0.05.
Table 5:
Determination of bumetanide in pure form in human urine ''spiking technique'' using
bumetanide-tungstophosphate-PVC membrane electrode.
Calibration graphs method
Taken
(M)
1.0 x 10-6
5.0 x 10-6
1.0 x 10-5
5.0 x 10-5
1.0 x 10-4
5.0 x 10-4
1.0 x 10-3
Mean ± S.D
( P= 0.05)
N
Variance
S.D.
S.E.
R.S.D.
Standard addition method
Recovery*
Found
[-log conc.] (M)
%
5.99
99.83
5.29
99.79
4.97
99.40
4.31
100.21
3.99
99.75
3.26
98.76
3.01
100.33
99.72 ± 0.525
7
0.276
0.525
0.198
0.526
*Average of three experiments.
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
Added
( M)
9.0 x 10-6
1.0 x 10-5
5.0 x 10-5
9.0 x 10-5
1.0 x 10-4
5.0 x 10-4
9.0 x 10-4
Found
[-log conc.] (M)
5.02
4.99
4.27
4.01
3.97
3.31
3.03
99.53 ± 0.394
7
0.155
0.394
0.149
0.396
Recovery*
%
99.49
99.80
99.28
99.12
99.25
100.27
99.48
Mean % of bumetanide
178
EL-TOHAMY ET AL
Table 6: Determination of bumetanide in pure form in human serum ''spiking technique'' using bumetanidetungstophosphate-PVC membrane electrode.
Calibration graphs method
Taken
(M)
Found
[-log conc.] (M)
1.0 x 10-6
5.0 x 10-6
1.0 x 10-5
5.0 x 10-5
1.0 x 10-4
5.0 x 10-4
1.0 x 10-3
Mean ± S.D
( P= 0.05)
N
Variance
S.D.
S.E.
R.S.D.
Standard addition method
Recovery*
%
Added
( M)
9.0 x 10-6
1.0 x 10-5
5.0 x 10-5
9.0 x 10-5
1.0 x 10-4
5.0 x 10-4
9.0 x 10-4
6.01
100.17
5.29
99.79
4.99
99.80
4.28
99.51
3.97
99.25
3.29
99.67
2.98
99.33
99.65 ± 0.315
7
0.099
0.315
0.119
0.316
Found
[-log conc.] (M)
5.03
4.97
4.29
4.01
3.99
3.32
3.04
99.73 ± 0.449
Recovery*
%
99.69
99.40
99.74
99.12
99.75
100.58
99.81
7
0.202
0.449
0.170
0.450
*Average of three experiments.
and in this range the electrode can be safely used for
bumetanide determination.
120
100
80
60
40
20
0
-20
0
10
20
30
40
Time/min
Fig. 5. Dissolution profile of bumetanide in tablets. All
values are the average of six determinations.
2. Effect of pH:
The effect of pH of the bumetanide solutions (10-6
,10-5, 10-4, 10-3, M bumetanide) on the electrode
potential was investigated. The solutions were acidified by the addition of very small volumes of HCl
then the pH value was increased gradually using
NaOH (0.1 or 1.0 M) for each pH value, the potential
was recorded and thus the potential–pH curves for
four bumetanide concentrations were constructed
(Fig.3). As is obvious, within the pH range 5-8, the
electrode potential is practically independent of pH,
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
3. Selectivity of the electrode:
The selectivity of the ion-pair associates based
membrane electrodes depends on the selectivity of
the ion-exchange process at the membrane-test
solution interface and the mobilities of the respective
ions within the membrane. The selectivity coefficients obtained by the separate solution method (15).
Table 2, showed that the proposed bumetanidetungstophsphate-PVC membrane is highly selective
toward bumetanide ion. The inorganic cations did not
interfere due to the differences in their mobilities and
permeabilities as compared with bumetanide cation.
In the case of sugars and amino acids, the high
selectivity is mainly attributed to the difference in
polarity and lipophilic character of their molecules
relative to bumetanide. The matched potential and
mixed solution methods( rather time consuming due
to the preparation of many solutions and performance of many steps) were only used in cases when
– log KpotBumet. was less than 3.5. It was demonstrated
by these methods that the electrode shows high
selectivity.
.
4. The electrode response in pharmaceuticals and
biological fluids:
The use of bumetanide drug in various fields,
from clinical to abuse in sports have necessitated an
PLASTIC BUMETANIDE MEMBRANE SENSOR
179
accurate and rapid, quantitative analysis in various
matrices (dosage forms and biological fluids). This
work proposed a fast, simple, easy, sensitive and
straightforward potentiometric method to determine
bumetanide in dosage forms and biological fluids
without the need for prior separation and preconcentration or derivatization procedures. The potential
of the bumetanide-tungstophosphate-PVC membrane
electrode showed no significant difference of response time between aqueous solution of pure drug and
its solutions from pharmaceutical preparations or
biological fluids (Tables 5,6).
6.
Conclusion
10.
The bumetanide-selective plastic membrane electrode based on bumetanide-tungstophosphate ion
association in a PVC matrix exhibited useful analyticcal characteristics for the determination of
bumetanide in pure form, pharmaceutical formulationsand biological fluids.
7.
8.
9.
11.
12.
References
1.
2.
3.
4.
5.
L. S. Goodman, A. Gilman, The Pharmacological Basis of
Therapeutic, 9th Edition, Mc Graw-Hill, New York, 1996, P.
701.
C. S. P. Sastry, T. N. V. Prasad, B. S. Sastry, E. V. Rao,
Spectrophotometric methods for the determination of some
diuretics using 3-methyl-2-bezothiazolinone hydrazone,
Analyst 113 (1988) 255.
L. Zivanovic, A. Agatonovic-Kustrin, M.Vasiljevic, D.
Radulovic, Investigation of Fe(III) chloride as a colour
reagent for the spectrophotometric determination of
bumetanide in the pure form and in preparations, Acta Pol.
Pharm. 49 (1992) 9-12.
E. González, A. Becerra, J.J. Laserna, Direct determination of
diuretic drugs in urine by capillary zone electrophoresis using
fluorescence detection, J. of Chromatogr. B, 687 (1996) 145150.
L. A. Marcantonio, W. H. R. Auld, G.G. Skellern,
Determination of the diuretic bumetanide in biological fluids
by high-performance liquid chromatography, J. Chromatogr.,
183 (1980) 118-123.
Saudi Pharmaceutical Journal, Vol. 14, Nos. 3-4, July-October 2006
13.
14.
15.
16.
17.
18.
bumetanide in plasma by high-performance liquid
chromatography, J. Chromatogr. Biomed. Appl., 434 (1988)
327-329.
D. Živanov-Stakić, L. J. Solomun, L. J. Živanović, Highperformance liquid chromatographic method for the
determination of bumetanide in pharmaceutical preprations, J.
Pharm. Biomed. Anal., 7 (1989) 1889-1892.
T. G. Wells, I. R. Hendry, G. L. Kearns, Measurement of
bumetanide in plasma and urine by high liquid
chromatography and application to bumetanide disposition, J.
Chromatogr. Biomed. Appl., 570 (1991) 235-242.
M. J. Legorburu, R. M. Alonso, R.M. Jimenez, E. Ortiz,
Quantitative determination of the loop diuretic bumetanide in
urine and pharmaceuticals by high-performance liquid
chromatography with amperometric detection,
J.
Chromatogr. Sci., 39 (2001) 425-430.
A. M. Lisi, G. J. Trout, R. Kazlauskas, Screening for diuretics
in human by gas chromatography-mass spectrophotometry
with derivatisation by direct extractive alkylation, J.
Chromatogr. Biomed. Appl., 563 (1991) 257-270.
A. M. Lisi, R. Kazlauskas, G. J. Trout, Diuretic screening in
human urine by gas chromatography-mass spectrometry: use
of a macro reticular acrylic copolymer for the efficient
removal of the co extracted phase-transfer reagent after
derivatization by direct extractive alkylation, J. Chromatogr.
Biomed. Appl., 581(1992) 57-63.
D. Carreras, C. Imaz, R. Navajas, M. A. Garcia, C.
Rodriguez, A. F. Rodriguez, R. Cortes, Comparison of
derivatization procedures for the determination of diuretics in
urine by gas chromatography-mass spectrometry, J.
Chromatogr. A, 683 (1994) 195-202.
P. Solich, C. K. Polydorou, M. A. Koupparis, C. E.
Efstathiou, Automated flow injection fluorimetric
determination and dissolution studies of bumetanide in
pharmaceuticals, Anal. Chim. Acta, 438 (2001) 131-136.
V. Sanz-Nebot, I. Toro, R. Berges, R. Ventura, J. Segura, J.
Barbosa, Determination and characterization of diuretics in
human urine by liquid chromatography coupled to
pneumatically assisted electrospray ionization mass
spectrometry, J. Mass Spectrom., 36 (2001) 652-657.
T. S. Ma, S. S. M. Hassan, Organic analysis using ion
selective electrodes, Vol. I and II, Academic Press, London,
1982.
G.D. Christian, Analytical Chemistry 16 th Edition, (2003)
403-404.
R. P. Buck, E. Lindner, Recommendations for nomenclature
of ion-selective electrodes, Pure Appl. Chem. 66 (1994) 25272536.
The United States Pharmacopoeia 25, NF 20, United States
Pharmacopoeia, Rockville, MD, P. 256-258.