J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43Spectrochemical Methods for the Determination of Sildenafil Citrate (Viagra) in Bulk Powder and in Pharmaceutical Dosage Form Analytical Chemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt
Received 17 October 2004 ; accepted 4 May 2005
Abstract: Three simple, accurate, sensitive and selective methods are described for the quantitative determination of sildenafil citrate (Viagra) in bulk powder and in pharmaceutical dosage form. Atomic absorption spectrometric method (method I) is based on precipitation of the ion associates formed from the reaction of the cited drug with silver nitrate (procedure A), copper acetate (procedure B) or ferric chloride (procedure C) standard solutions. The formation and solubility of the solid complexes at the optimum conditions of pH and ionic strength values have been studied. The method depends on direct determination of the ions in the precipitate or indirect determination of the ions in the filtrate by atomic absorption spectroscopy. The optimum conditions for precipitation were carefully studied. Rectilinear calibration graphs were obtained in the range of 10-80 ng ml-1 for the investigated drug. Limits of detection and quantitation ranged from 1.911 to 2.220 and from 4.441 to 5.986 ng ml-1, respectively. The molar ratios of the formed chelats were determined by Job's method and their association constants were also calculated. Spectrophotometric method (method II) is based on the ion-pair complex reaction of Viagra with methyl orange (procedure D) or bromophenol blue (procedure E) in buffered aqueous solution. The chromogen, being extractable with chloroform, could be measured quantitatively at 425 and 410 nm with methyl orange and bromophenol blue, respectively. All variables were studied to optimize the reaction conditions. Regression analysis of Beer's plot showed good correlation in a general concentration range 2-20 µg ml-1. Derivative spectrophotometric method (method III) has become a good practical analytical method in the general laboratory because of the rapid progress in the general technology, for such reasons, the first derivative (procedure F) and second derivative (procedure G) spectra of sildenafil citrate in distilled water were recorded and the derivative maxima were related to the concentration. Regression analysis of Beer's plot showed good correlation in a general concentration range 1-10 µg ml-1. The developed methods (I, II and III) were applied successfully for the determination of the studied drug in its pharmaceutical dosage form with a good precision and accuracy compared to the reported method as revealed by t-and F-tests. Key words:
Sildenafil Citrate; Spectrochemical Methods; Bulk
Sildenafil citrate (Viagra®), used for the treatment of erectile dysfunction
(ED), is rapidly becoming one of the most popular and widely used drugsthroughout the United States and Europe. The extensive use of sildenafil isexemplified by the fact that 6 million prescriptions for this agent were writtenduring the first 6 months following its introduction . Contrary to popular belief,sildenafil is not an aphrodisiac, does not work in the absence of sexual arousal,and does not make a potent man more virile . Sildenafil citrate is designatedchemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin -5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate.
Viagra is rapidly absorbed after oral administration, with absolute
bioavailability of about 40% its pharmacokinetics are dose-proportional over therecommended dose range. It is eliminated predominantly by hepatic metabolismand is converted to an active metabolite with properties similar to the parent,Sildenafil .
Few papers have been reported for determination of sildenafil citrate
include, voltametry [4, 5], liquid chromatography , high performance liquidchromatography [7, 8] and spectrophotometry [9-12].
Although atomic absorption spectrometry is a rapid method and has very
low detection limits which can not be reached by most of other methods, it has notbeen applied yet to the determination of sildenafil citrate. The present workincludes new direct and indirect methods for determination of sildenafil citrate. The present work represents the utilization of silver nitrate, copper acetate andferric chloride as reagents for the determination of the studied drug by direct andindirect atomic absorption spectrometric measurements. The methods proved tobe very sensitive and accurate for the determination of sildenafil citrate in bulkpowder and in pharmaceutical dosage forms.
Derivative spectrophotometry has proved to be a good approach for
determination of a drug in presence of matrix interference , another drug or degradation product . Consequently, a first derivative would eliminate aconstant interference and a second derivative would eliminate a linearinterference.
Recently, one spectrophotometric method reported for determination of
sildenafil citrate via its reaction with bromocresol green and with chromoxanecyanine R in aqueous acidic buffer solution . Except this work, no data wereavailable in the literature for the selective determination of the cited drug.
Moreover, the present work aims at developing a simple and rapid
selective atomic absorption spectrometric, spectrophotometric and derivativespctrophotomeric procedures for the determination of sildenafil citrate (Viagra®)in bulk power and in pharmaceutical dosage forms. Experimental Apparatus
Spectronic TM GenesysTM, UV/VIS spectrophotometer interfaced to an IBMcomputer loaded with the WinspecTM application software.
A Shimadzu atomic absorption flame spectrophotometer model AA.640-13. For AAS, silver, copper and iron were measured at wavelengths 328.1, 327.7and 240.7 nm, respectively, slit width 0.2 nm, relative noise 1.0, detection
J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43
limit 0.01 µg/ml, lamp current 7 mA and integration time 3 s. The flame usedwas an acetylene-air mixture.
The pH values of solutions were measured using an Orion Research Model601A digital pH-meter.
All calculations were carried out on IBM computer using Microsoft excel
2002 for windows ME. SMAC program  was used for all statistical methods. Chemicals and Reagents
All solvents and reagents were of analytical reagent grade, double distilled
water was used throughout. Sildenafil citrate was generously supplied by theirrespective manufacturers (Pfizer Co., Egypt. Under Authority of Pfizer INC.,U.S.A). 0.025 M silver nitrate (0.524% W/V solution), 0.01 M copper acetate(0.2% W/V solution) and 0.01 M ferric chloride (0.18% W/V solution) wereAldrich products. Methyl orange solution; 0.15 g% in 40% aqueous methanol. Bromophenol blue; 0.1 g% in 50% aqueous ethanol. Teorell and Stenhagen buffersolutions  of pH range (2-10) were used for pH adjustment. Pharmaceutical Preparation
Viagra® tablets (Pfizer Co., Egypt. Under Authority of Pfizer INC., U.S.A)
labeled to contain 50 mg sildenafil citrate per tablet. Standard Preparations
Stock solutions containing 3 µg ml-1 sildenafil citrate was prepared in
distilled water. Working standard solutions containing 10-80 ng ml-1, 2-20 µg ml-1and 1-10 µg ml-1 for atomic absorption spectrometric, spectrophotometric andderivative spectrophotometric procedures, respectively, were prepared by suitabledilution of the stock solutions with distilled water. Procedures
1. For Atomic Absorption Spectrometric Method (Method I)
1.1. Atomic Absorption Spectrometric Method Utilizing Silver
To aliquots of sildenafil citrate stock solution (equivalent to 10-60 ng ml-1),
2.00 ml of 0.025 M silver nitrate solution was added. Solutions were protectedfrom light, shaken and filtered (whatman No.44). The precipitates were washedwith redistilled deionized water until free of silver (I).
The precipitates obtained above were dissolved in a minimum amount of
dilute ammonia solution and completed to 25 ml with redistilled deionized water. A 2.00 ml of the resulting solutions was diluted to 25 ml with redistilleddeionized water.
The filtrates and washings were collected in a 100 ml volumetric flask and
completed to volume with redistilled deionized water. A 10.00 ml of the resultingsolution was diluted to 100 ml with redistilled deionized water. A blank (omitting addition of drug) was prepared and the absorbance wasmeasured at the flaming conditions; wavelength 328.1 nm, lamp current 7 mA, slitwidth 3.8 A, air flow rate 10L/min and acetylene flow rate 2.6 L/min. Silver (I)concentrations were calculated from a calibration curve. 1.2. Atomic Absorption Spectrometric Method Utilizing Copper
To aliquots of sildenafil citrate stock solution (equivalent to 10-80 ng ml-1),
2.00 ml of copper acetate solution was added. Solutions were well shaken, filtered(whatman No.44), and the precipitates were washed with redistilled deionizedwater until free of copper (II).
Precipitates were dissolved in a minimum amount of dilute ammonia
solution and completed to 100 ml with redistilled deionized water. A 5.00 ml ofthe resulting solution was transferred into a 50 ml volumetric flask and completedto volume with redistilled deionized water.
The filtrates and washings were collected in a 100 ml volumetric flask and
completed to volume with redistilled deionized water. Five ml of the resultingsolution was diluted to 100 ml with redistilled deionized water. A blank (omitting addition of drug) was prepared and the absorbance wasmeasured at the flaming conditions; wavelength 327.7 nm, lamp current 7 mA, slitwidth 3.8 A, air flow rate 10L/min and acetylene flow rate 2.3 L/min. Copper (II)concentrations were calculated from a calibration curve. 1.3. Atomic Absorption Spectrometric Method Utilizing Iron
To aliquots of sildenafil citrate stock solution (equivalent to 10-80 ng ml-1),
two ml of ferric chloride solution was added, shaken well and filtered (whatmanNo.44). The precipitates were washed with redistilled deionized water until free ofiron (III).
The precipitates were dissolved in a minimum amount of dilute ammonia
solution and completed to 25 ml with redistilled deionized water. A 2.00 ml of theresulting solutions was diluted to 50 ml with redistilled deionized water. J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43
The filtrates and washings were collected in a100 ml volumetric flask and
completed to volume with redistilled deionized water. A 5.00 ml of the resultingsolution was diluted to 100 ml with redistilled deionized water.
A blank (omitting addition of drug) was prepared and the absorbance was
measured at the flaming conditions; wavelength 240.7 nm, lamp current 7 mA, slitwidth 3.8 A, air flow rate 10L/min and acetylene flow rate 2.5 L/min. Iron (III)concentrations were calculated from a calibration curve.
2. For Spectrophotometric Method (Method II)
2.1. Spectrophotometric Method Utilizing Methyl Orange
One milliliter of sildenafil citrate stock solution was pipetted into a 100
separating funnel containing 3 ml buffer pH 2.3. Then 2 ml of 0.1% W/V M.O.
in 40% aqueous methanol was added. This was mixed well and three 8 ml
quantities of chloroform extracted. The extracts were collected in a 25 mlvolumetric flask and diluted to volume with chloroform. Approximately 0.1 ganhydrous sodium sulphate was added, shaken for about 1 min, filtered and thefirst portion of the filtrate rejected. The absorbance of the resulting solution at 425nm against a similarly treated reagent was measured. 2.2. Spectrophotometric Method Utilizing Bromophenol Blue
Aliquots containing 2-20 µg ml-1 of sildenafil citrate stock solution were
pipetted into a 100 separating funnel containing 3 ml buffer pH 2.9 and 5 ml ofbromophenol blue and completed to 25 ml with distilled water.
The mixture was extracted with 20 ml chloroform (added in three portions)
and the collected extracts were transferred into 25 ml calibrated flask. Then 2 mlethanol was added and completed to volume with chloroform. The yellow coloured chloroformic extract was measured against blank atwavelength 410 nm.
3. For Derivative Spectrophotometric Method (Method III)
3.1. First Derivative Spectrophotometric Method
Aliquots of the standard or/ assay solution were transferred (to give final
concentration ranged from 1-10 g ml-1) into a set of 25-ml volumetric flasks. Dilute with distilled water. The first (1D) derivative spectra was recorded for eachsolution between 200.0–350.0 nm and related their amplitudes to theconcentration. 3.2. Second Derivative Spectrophotometric Method
Aliquots of the standard or/ assay solution were transferred (to give final
concentration ranged from 1-10 g ml-1) into a set of 25-ml volumetric flasks. Dilute with distilled water. Second (2D) derivative spectra for each solution
between 200.0–350.0 nm was recorded and related their amplitudes to theconcentration.
An accurately weighed amount, equivalent to 10 mg of Viagra® tablets from
composite of 20 powdered tablets, was transferred into a 100-ml calibrated flaskand diluted to the mark with the appropriate solvent, sonicated for 20 min andfiltered off to obtain stock solutions. Further dilutions were made to obtain samplesolutions for methods I, II and III, respectively, then the general procedures werefollowed.
Drug and metal solutions of equimolar concentrations (1x10-4M) were
prepared. Aliquots of each solution were added in different ratios to a series of 10ml calibrated flasks, so that the total volume of both is 5 ml. The pH is adjustedusing 1 ml buffer solution  and then the volume is completed with theappropriated solvent. The relative absorption intensity of each formed chelate ismeasured at its respective maxima .
According to Job's method of continuous variation , an equimolar
solution of sildenafil citrate and methyl orange or bromophenol blue (12.5x10-5M)were prepared. A series of extraction experiments were carried out using 10 mlportions of the solutions in different complementary proportions (from 0+10 to10+0 inclusive) using the suitable buffer in each case. Results and Discussion
Slightly alkaline (pH 7.8-8.3) alcoholic solutions of sildenafil citrate gave
white coagulated precipitates with silver nitrate (procedure A), green bluishprecipitates with copper acetate (procedure B) and reddish brown precipitates withferric chloride (procedure C). These precipitates form the basis of the micro-quantitative determinations of sildenafil citrate. Ag (I), Cu (II) or Fe (III) contentscan be determined either directly in the precipitate or indirectly in the filtrate byatomic absorption spectrometry (method I).
Ion-pair extraction spectrophotometric method has received considerable
attention for quantitative estimation of many pharmaceutical compounds. In thisstudy methyl orange and bromophenol blue being anionic dyes, form withsildenafil citrate, in acidic pH, a yellow colored ion-pair of complexes which aresoluble in chloroform and can be measured at 425 and 410 nm for methyl orange(procedure D) and bromophenol blue (procedure E), respectively (Figure 1). J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43Wavelength (nm) Fig 1. Absorption spectrum of sildenafil citrate (- -), bromophenol blue (__),
methyl orange (….) ion pair complexes after extraction with chloroform. Final
concentration of sildenafil citrate = 16 gml-1
Generally speaking, table excipients mostly exhibit some kind of
interference during direct absorbance measurement (the absorption spectrum ofsildenafil citrate in distilled water is shown in Figure 2). Wavelength (nm) Fig 2. Absorption spectrum of 16 gml-1 sildenafil citrate in distilled water
Constant interference could be completely eliminated by recording the
first derivative (1D) of the UV absorption spectrum (procedure F). Consequently,the 1D spectrum in distilled water between 200.0 – 350.0 nm was recorded asshown in Figure (3). First derivative -0.02 Wavelength (nm) Fig 3. First derivative spectrum of 16 gml-1 sildenafil citrate in distilled water
A proportional relationship exists between the measured amplitude at the
specified wavelength and the concentration of the drug. Also, second derivativespectrum (2D) of the UV absorption spectrum (procedure G) can eliminate anylinear interference. Similarly, the 2D spectrum in distilled water was recordedbetween 200.0 – 350.0 nm as shown in Figure (4) and the 2D amplitudes at thespecified wavelength were related to the concentration sildenafil citrate. derivative Second -0.04 Wavelength (nm) Fig 4. Second derivative spectrum of 16 gml-1 sildenafil Optimization of the Reaction Conditions For Atomic Absorption Spectrometric Method (Method I)
Addition of the recommended amount of ethyl alcohol is to enhance the
solubilization of the drug and coagulation of the precipitates. Larger volumes ofalcohol must be avoided to prevent solubilization of the formed precipitates.
In order to study the effect of pH on precipitation, buffer solutions
covering the acid to alkaline range were tried. Acid media have a solubilizingeffect on the precipitate leading to lower results for the direct technique andhigher ones for the indirect technique while higher alkali media precipitate themetal as its oxide or hydroxide leading to higher results for the direct technique. The optimum pH was found to be slightly alkaline (pH = 7.8 – 8.3).
Considering metal ion concentration effect on precipitation, 2 ml of the
precipitating solutions was found to be sufficient for complete precipitation.
Regarding the temperature effect on precipitation, room temperature was
found to be the most efficient. Higher temperature show solubilizing effect on theprecipitate producing lower results for the direct technique and higher ones for theindirect technique. J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43
Job's method of continuous variation  was used to study the molar
ratios of the formed chelates. The method revealed 1:1, 2:1 and 3:1 sildenafilcitrate to silver (I), copper (II) and iron (III), respectively.
The stability constants of the formed chelates were calculated using the
= A/Aex CX / (CM – A/Aex CX) (CL – nA/Aex CX)n
Where is the stability constant of the formed chelate, M indicates metal,
L indicates ligand, n =X/(1-X) where X is the mole fraction of the ligand at themaximum of the continuous variation curve. A/Aex is the ratio of the observedabsorbance to that indicated by the tangent for the same wavelength. CM and CLare the concentrations of the metal and the ligand, respectively, Cx = CL/n = CM.
The calculated stability constants for the formed chelates (Table 1) are
ranging from 109.1358 x 10-7 to 158.2658 x 10-7 indicating good stability of theformed chelates. Table 1. Association constants of the formed chelates between the suggested metal and sildenafil citrate using atomic absorption spectrometric method
Job's method of continuous variation  indicated molar ratios of 1:1, 2:1
and 3:1 sildenafil citrate to silver (I), copper (II) and iron (III), respectively(Figure 5). Vd/Vd+Va Fig 5. Continuous variation plot of sildenafil citrate with silver (__), For Spectrophotometric Method (Method II)
The effect of pH was studied by extracting the colored complex formed in
the presence of Teorell and Stenhagen buffer  of different acidic pH values. Accordingly Table 2 shows that a pH below 3 is recommended and the best
results were found at pH 2.3 and 2.9 for methyl orange and bromophenol blue,respectively. Table 2. Effect of different acidic pH values on the formation of the ion-pair complex between the suggested dyes and sildenafil citrate
* Torell and Stenhagen buffer. ** No color was observed in the organic layer at pH 5.
The amount of dyes should be sufficient and the excess has no effect on
The produced yellow colour was stable up to 48 h without any change in
A number of immiscible organic solvents were tested so as to provide an
applicable extraction procedure. Table 3 shows that the yellow colored product isextractable only with methylene chloride and chloroform.
Although methylene chloride was found to be slightly better, owing to its
high volatility chloroform was used throughout this work. Table 3. Effect of different solvent on the extraction efficiency of the ion-pair complex between methyl orange or bromophenol blue with sildenafil citrate J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43Quantification and Validation of Assay Procedures
To study the accuracy of the proposed methods, synthetic mixtures
containing various amounts of drug were prepared and analyzed by the proposedatomic absorption spectrometric (A, B and C), spectrophotometric (D and E) andderivative spectrophotometric (F and G) methods. Also, the C.V. % wascalculated from the results of recovery experiments (Table 4). Table 4. Parameters for calibration curves construction
Method (I) Atomic absorption spectrometric methodProcedure ADirect
0.265 0.705 0.9997 0.9994 1.911 4.441 0.39
-1.027 0.963 0.996 0.9992 2.220 4.850 0.91
0.911 0.521 0.9997 0.9994 2.211 4.747 0.80
0.588 0.456 0.9996 0.9992 1.993 5.986 0.57
0.368 0.471 0.9995 0.9990 2.101 4.802 0.67
0.995 0.985 0.9998 0.9996 1.992 4.556 0.58
Method (II) Spectrophotometric methodProcedure D
2-20 g ml-1 0.0258 0.3652 0.9996 0.9992 0.251 0.854 0.59
2-20 g ml-1 0.0304 0.0987 0.9997 0.9994 0.131 0.214 0.51
Method (III) Derivative spectrophotometric methodProcedure
ml-1 0.0084 0.0359 0.9997 0.9994 1.727 0.598 0.25
1-10 g ml-1 -0.0078 0.0145 0.9998 0.9996 0.875 0.394 0.27
a: intercept; b: slope; r: correlation coefficient; r2: coefficient of determination; LOD: limit ofdetection; LOQ: limit of quantitation.
The accuracy of the proposed procedures were established by comparing
the results of analysis of the proposed procedures with the reported method ,the suggested methods are equally precise and accurate to the reported method(Table 5).
The precision of the methods were tested by triplicate analysis of different
concentrations. For comparison, the reported method  was applied for thedetermination of the intact drug. Statistical analysis of the results obtained(Table 5) indicated that the proposed procedures were as accurate and precise asthe reported method. Table 5. Statistical analysis of the results obtained using the proposed methods and reported method for analysis of authentic sildenafil citrate
* The t- and F- values refer to comparison of the proposed method with the official or reportedmethods. Theoretical values at 95% confidence limit t = 2.23 and F=5.79.
The proposed procedures have the advantage that most of the assays are
performed in the visible region from the UV-absorbing interferences that might beco-extracted from dosage forms. Also, before dealing with the analysis of thepharmaceutical preparations, the effects of common additives, adjuvants andexcepients on the proposed method were experimentally studied. The resultsobtained revealed that hydroxypropyl metyl cellulose, titanium dioxide, lactoseand triacetin do not interfere (Table 6). Table 6. Assay of the studied sildenafil citrate in presence of common excipients
* The amount of excipients added per 50 mg of drug
By applying the proposed analytical procedures, the limit of detection was
detected both practically and by mathematical method. It was calculatedaccording to the recommendation for LOD for spectrochemical methods whichwas published in 1987 by international union of pure and applied chemistryIUPAC . The practically determined LOD. did not show significant differentfrom that of calculated one (Table 4). J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43
It can be calculated using SMAC program , but it must be also
determined practically by analysis of samples with known concentrations ofanalyte and by establishing the minimum level at which the analyte can bedetermined with acceptable accuracy and precision (Table 4).
The practically determined LOQ. was showed significant different from
that of calculated one as it is little higher than that of calculated ones.
A linear correlation was found between absorbance and concentration of
sildenafil citrate in the range 10-80 ng ml-1 for method I (A, B and C), 2-20 µgml-1 for method II (D and E) and 1-10 µg ml-1 for method III (F and G). Thelinearity range can be determined by making a plot of absorbance as a function ofconcentrations for both drug and reagents (Table 4).
The ruggedness of an analytical method is the degree of reproducibility of
test results obtained by the analysis of the same sample under a variety ofconditions while robustness of analytical method is a measure of its capacity toremain unaffected by small but deliberate variations in method parameters.
Both ruggedness and robustness were determined by assessment of the
degree of reproducibility of the regression analysis obtained by determination ofthe same standard samples in different days as the regression equation wasdetermined at each max. along different four weeks (Table 7), there is nosignificant difference between the regression equations that determined along thefour weeks, this provide that these methods used for determination of the studieddrug are reproducible and not affected by variations in the day of analysis. Table 7. Study of the degree of reproducibility of the regression analysis obtained by determination of the same standard samples in different days
0.0023 0.0035 0.0036 0.0021 0.0029 0.0008
10-60 ng ml-1 0.0003 0.0010 -0.0010 0.0006 0.0002 0.0009
2-20 g ml-1 0.0017 0.0021 0.0014 0.0018 0.0018 0.0003
2-20 g ml-1 -0.0008 -0.001 -0.0011 -0.0011 -0.001 0.0001
1-10 g ml-1 0.0035 0.0019 0.0035 0.0028 0.0029 0.0007
1-10 g ml-1 0.0012 0.0018 0.0018 0.0013 0.0015 0.0003
Also, the ruggedness and robustness of these developed analytical methods
were determined by studying the effect of changing the used instrument obtained,as the analysis of sildenafil citrate was repeated using another spectrophotometer(JENWAYTM). Table 8, shows that the results obtained from instrument (I) are equally preciseand accurate to that obtained from instrument (II) as there is no significant
difference between calculated t or F values and tabulated ones, this showed thatchanging the instrument did not affect the test results and assure itsreproducibility. Table 8. Comparison of the recovery experiment of sildenafil citrate using spectrophotometer (I) and spectrophotometer (II)
At P=0.05, t = tabulated = 2.45, F = tabulated = 9.28
Analysis of Pharmaceutical Formulations
The proposed atomic absorption spectrometric, spectrophotometric and
derivative spectrophotometric methods were applied to the determination ofsildenafil citrate in Viagra® tablets and (Table 9). The results were comparedstatistically with those obtained by applying the reported methods . In the t and F tests, no significance difference was found between the calculatedand theoretical values (95% confidence) of the proposed and reported methods. This indicates similar precision and accuracy. Data of Table 9 suggested that thepresent procedures could be applied to the assay of this drug in its single dosageform without interference. Frequently encountered common ingredients offormulations were found not to interfere. The obtained high-intensity absorption bands and the very low reagentbackground make this procedure suitable for the routine quality control analysisof the investigated sildenafil citrate drug with minimum interference. J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43Table 9. Determination of sildenafil citrate in Viagra® tablets
The t- and F- values refer to comparison of the proposed method with the officialor reported methods. Theoretical values at 95% confidence limit t = 2.23 and F=5.79. Conclusion
Simple, rapid, accurate sensitive and selective atomic absorption
spectrometric, spectrophotometric and derivative spectrophotometric methodswere developed for the analysis of sildenafil citrate (Viagra®) via its reaction withthe suggested reagents. It can be obviously seen that the spectrophotometricmethods have higher max values than the reference Amax method. This is adecisive advantage since the interference from the associated ingredients shouldbe far less at higher wavelengths than at lower wavelengths. Moreover, all theapplied methods are much more sensitive than reference method especially theatomic absorption spectrometric method of analysis. The derivativespectrophotometric method is the simplest. The proposed procedures could beapplied to quality-control analysis of the investigated drug. The procedures couldalso be automated, the ongoing work is directed to develop and validate thissystem. References
1. Schwarz U.R., Walter U., and Eigenthaler M., (2001), BiochemPharmaco 62(9): 1153.
2. Terrett K., et.al., (1996), Bio. Med. Chem. Lett. 6(15): 1819.
3. Ichiro S., et.al., (2002), Europ. J. Pharmaco. 437(3): 155.
4. Berzas J.J., Rodriguez J., Castañeda G., and Villaseñor M.J., (2000),
Anal Chimica Acta, 417(2): 143.
5. Rodr ´guez J., Berzas J.J., Castan~eda G., and Rodr ´guez N., (2004),
6. Dinesh N.D., Vishukumar B.K., Nagaraja P., Made Gowda N.M., and
Rangappa K.S., (2002), J. Pharm. Biomed. Anal. 29(4): 743.
7. Daraghmeh N., Al-Omari M., Badwan A.A., and Jaber AMY, (2001),
J. Pharm. Biomed. Anal., 25(3-4): 483.
8. Shim H., Lee E.J., Jung Y.H., Kim S.H., Kim S.H., Yoo M., Kwon
J.W., Kim W.B., and Lee M.G., (2002), J. Pharm. Biomed. Anal. 30(3): 527.
9. Alt okka G., Atkosar Z., Sener E., and Tunçel M., (2001), J. Pharm.Biomed. Anal., 25(2): 339.
10. Al-bojuk, et.al., (2001), Heterocycles. 55(9): 1789.
11. El-Abadelah, et.al., (2002), J. Heterocycl. Chem. 39(5): 1055.
12. Dinesh N.D., Nagaraja P., Made Gowda N.M., and Rangappa K.S.,
(2002), Talanta, 57(4): 757.
13. Mabrouk M.M., Salem H., Radwan M.F., and Kaood T.S., (2003),
Egypt J. Biomed. Sci. 12: 141.
14. Salem H., (1999), Chinese Pharm. J., 51: 123.
15. Salem H., El-Maamli M., El-Sadek M., and Aboul-Kheir A., (1994),
Zag. J. Pharm. Sci., 3(1): 115.
16. Meiere P.C., and Zund R.E., (1993), Statistical Methods In Analytical
17. Pesez M., and Bartos (eds) J., (1974), Colorimetric and FluorimetricAnalysis of Organic Compounds and Drugs, p. 628, Marcel Dekker,Inc., New York.
18. Rose J., (1964), Advanced Physico-Chemical Experimental, Pittman,
19. Sawyer D.T., Heinman W.R., and Beebe J.M., (1984), ChemistryExperiments for Instrumental Methods, Wiley J., New York, p. 205.
20. Carr G.P.R., and Wahlich J.C., (1994), "International PharmaceuticalProducts Registration", Ch.8 (Anthony C. Cartwright and Brian R. Matthews, Eds.), pp.247-287 Ellis Horwood Limited. J. J. Appl. Sci., 2006: Vol. 8, No. 1, 28-43
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