D BHARATH KUMAR MPA IV SEM RESEARCH WORK PRESENTATION.ppt

D BHARATH KUMAR MPA IV SEM RESEARCH WORK PRESENTATION.ppt

1. DETERMINATION OF CITALOPRAM BY RP -HPLC & IT’S
STABILITY INDICATIVE STUDIES
Dissertation submitted to Faculty of Pharmacy
PALAMURU UNIVERSITY
MAHABUBNAGAR –500 002
In partial fulfillment for the award of the degree of
MASTER OF PHARMACY
Submitted by
D.BHARATH KUMAR
(Reg.No. 3120885008)
Under the guidance of
M. VENKATESH, M.Pharm
Associate Professor
Department of Pharmaceutical Analysis
DHANVANTHRI COLLEGE OF PHARMACEUTICAL SCIENCES
MAHABUBNAGAR, TELANGANA STATE-509002
February-2024

2. CONTENTS
CHAPTER NO TITLE
I
INTRODUCTON & DRUG PROFILE
II LITERATURE REVIEW
III
AIM, OBJECTIVES & PLAN OF WORK
IV EXPERIMENTAL WORK
V RESULTS AND DISCUSSION
VI SUMMURY & CONCLUSION
VII
BIBLIOGRAPHY

3. Classification of analytical methods
UV VISIBLE SPECTROPHOTOMETER
HPLC
Analytical Chemistry
1
1. INTRODUCTON & DRUG PROFILE
1. INTRODUCTON

4. UV-Visible Spectroscopy
2
UV 2310 Electronics India
Lightsource Tungsten lamp
Deuterium lamp
MonochromatorGrating
Detector Silicon Photodiode
wavelength
range
200-400nm
UV 2310 ELECTRONICS INDIA
SPECIFICATIONS
Components:
Sourceoflight
Monochromatic.
Samplesolutionin
corvette
Photodetector
Readoutdevice

5. High Performance Liquid Chromatography (HPLC)
3
Components:
1.Reservoir
2.Filter
3.Pump
4.PressureGauge
5.Sample Injection valve
6.ColumnOven
7.GuardColumn
8.AnalyticalColumn
9.Detector.
10.Recorder(Integrator,PC)
LC 10 AT VP SHIMADZU HPLC
SPECIFICATIONS
PUMP LC 10 AT VP
UV–VISDETECTOR UV 2000
SYSTEMCONTROLLER SN 4000
SOFTWARE AUTOCHRO-3000
LC 10 AT VP SHIMADZU HPLC

6. AnalyticalMethodDevelopment
4 .5,6,7
A good analytical method development strategy should require many experimental runs to
achieve the desired final result.
Finally method development should be simple ,Accurate and Precise.
The important factors, for quantitative analysis, are
Sample Physico -chemical properties, its solubility, selection of Instrument ,Development of
the new method based on above characteristics and finally optimization of the developed
method.
Optimization :
The initial sets of conditions from the first stages of development are improved in terms of
resolution and peak shape, plate counts, asymmetry, capacity factor, elution time, detection
limits, limit of quantitationand overall ability to quantify the specific analyte of interest.
AnalyticalMethodDevelopment &Validation

7. Method validation -As per ICH
7
“Establishing documented evidence which provides a high degree of assurance
that a specific activity will consistently produce a desired result or product
meeting its predetermined specifications and quality characteristics”.
ICH Method validation parameters
For chromatographic methods-The Validation parameters are
•Specificity
•Linearity
•Accuracy
•Precision
•Limit of Detection
•Limit of Quantitation
•Robustness
•System suitability
AnalyticalMethodDevelopment & Validation

8. DRUG CATEGORY : Citaloprambelongs to a class of antidepressant agents known
as selective serotonin-reuptake inhibitors (SSRIs)
STRUCTURE :
IUPAC NAME : 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-
benzofuran-5-carbonitrile
PHYSICOCHEMICAL PROPERTIES :
Molecular mass : 324.3919
Solubility : Citalopram hydrobromide is sparingly soluble in water ,insoluble in
ethanol.
BRAND NAMES : Celexa ,Celapram,Celica
1.5 Drug Profile
8
1. INTRODUCTON & DRUG PROFILE
CITALOPRAM

9. 2.LITERATUREREVIEW
G.H. Ragab et al (2019) A novel, fast and sensitive HPLC method has been developed for the
simultaneous bioanalytical determination of Donepezil hydrochloride (DON) and Citalopram
hydrobromide (CTP) in raw materials, spiked human plasma and tablets.Elution of both drugs
was achieved with very good resolution using a RP-C18 chromatographic column, samples were
analyzed using Hypersil Gold (100 mm ×4.6 mm), 5 μm particle size column and an isocratic
binary mobile phase consists of phosphate buffer (0.05 M): acetonitrile (65:35). A Diode array
detector at wavelength 232 nm was used. Chromatographic separation was within a short run
time (less than 7 minutes) for both drugs.
9
.
Amit Suryakant Tapkir et al (2016) A simple, fast, accurate and precise method has been
developed UV-Vis spectrophotometric method for the estimation of citalopram HBr in bulk and
pharmaceutical dosage form. The solvent used was distilled water and the absorption maxima. (λ
max) of drug was found 239 nm. A linear response was observed in the range of 4-20 μg/ml with
a regression coefficient of 0.999. Citalopram HBr was subjected to acid hydrolysis, alkali
hydrolysis,oxidation, photo and thermal degradation. The citalopram shows relative high thermal
and photo stability.i.e.(0.15% at 48 hours and 0.21% at 72 hours) as compared to other stability
conditions. The reversed-phase high performance liquid chromatography method has been
developed for citalopram HBr. The separation and degradation product was carried out on C18
column Phenomenex-250×4.6mm×5μm using mobile phase consisting of acetonitrile: water
(75:25%v/v), at a flow rate of 1.5 ml/min and with detection wave length 239 nm. The retention
times for citalopram HBr was 5.56 min. The calibration plots were linear over the concentration
range of 10-60 μg/ml with regression coefficient of 0.999 for citalopram HBr.
10

10. YagnambhatlaRajendraetal(2015)NewmethodwasestablishedforestimationofCitalopram
byRP-HPLCmethod.Methods:ChromatogramwasrunthroughHypersilBDSC18,250mmX
4.6mm,5μmcolumn.MobilephasecontainingbufferandMethanolintheratioof60:40was
pumpedthroughcolumnataflowrateof1ml/min.Temperaturewasmaintainedat450C.
OptimizedwavelengthforCitalopramwas239nm.Results:RetentiontimeofCitalopramwas
foundtobe4.670min.The%purityofCitalopramwasfoundtobe100.4%.Thesystem
suitabilityparametersforCitalopramsuchastheoreticalplatesandtailingfactorwerefoundtobe
6.906.6,1.67.ThelinearitystudyforCitalopramwasfoundinconcentrationrangeof20μg-60μg
correlationcoefficient(r2)wasfoundtobe0.999%,%RSDforrepeatabilitywas0.86,%RSD
forintermediateprecisionwas0.47.Theprecisionstudywasprecise,robustandrepeatable.LOD
valuewas0.598,andLOQvaluewas1.81.
11
2.LITERATUREREVIEW
CH.AjayKumaretal(2014)Theobjectiveofthecurrentworkistodevelopasimple,efficient,
economicalandLC-MScompatibleRP-HPLCPDAmethodfortheanalysisofCitalopram
Hydrobromideinbulk,dosageformsandindissolutionsamples.Sampleswereseparatedon
AgilentEclipseC18column(150x4.6mm,5µm)withmobilephasecomposedof10mM
Ammoniumacetate:methanol(35:65v/v)inisocraticmode.Thedetectionwavelengthwasfixed
at239nm.TheretentiontimeofCitalopramHydrobromidewas3.1minandthemethodshoweda
goodlinearityintheconcentrationrangeof5-25µg/mLwithacorrelationcoefficientof0.997
12

11. 2.LITERATUREREVIEW
AsadRazaandTariqMahmoodAnsarietal(2014)Afast,sensitiveandextractionfree
spectrophotometricmethodforthequantitativedeterminationofcitalopramhydrobromidein
pharmaceuticalrawandtabletformulationshasbeenproposed.Thenewlyproposedmethodis
basedonthechargetransferreactionbetweencitalopramaselectrondonorandchloranilas
electronacceptor.Thechargetransfercomplexofcitalopramandchloranilshowsλmaxat550
nminmethanol.Theexperimentalconditionssuchasreactiontime,temperature,stoichiometry
ofthecoloredcomplexhavebeenoptimized.Thedevelopedmethodallowsthedetermination
ofcitalopramhydrobromideoveraconcentrationrangeof1-25µg/ml.Theproposedmethodis
usedtodeterminethecitalopramintabletdosageforms.Nointerferencehasbeenobservedfor
excipientsandadditivesintabletformulations
13
.

12. K. Sujathaet al (2013)An accurate high performance liquid chromatographic method was
developed for quantification of citalopram in its tablet dosage forms. Ideal separation of the drug
was achieved on an Agilent Eclipse XDB C
18column (150 x 4.6 mm; 5m) by eluting with a
mobile phase consisting of a mixture of acetate buffer (pH 4.5) and acetonitrile (65:35 v/v) at a
flow rate of 1.0 mL/min. The drug in the eluates was monitored by U V detection at 240 nm.
Under optimized conditions, the retention time obtained for the drug was 3.72 min. The relevant
calibration plot was linear in the concentration range of 25-150 µg/mL of the drug. The validation
of the method was done by following the ICH guidelines.
14
2.LITERATUREREVIEW
C. Saravanan et al (2012)
31
Aim of the present investigation was to develop and validated a
new, simple, sensitive, selective and precise High Performance Thin Layer Chromatograpic
(HPTLC) method for the determination of Citalopram HBr in tablet dosage form. TLC
aluminium sheets pre coated with silica gel 60F-254 were used as the stationary phase and
Methanol:Water:Ethyl acetate (4:2:4) was used as the mobile phase for the linear ascending
development carried out in twin trough glass chamber at room temperature (25±20C).
Spectrodensitometric scanning and analysis in absorbance mode at 240nm were carried out using
CAMAG TLC Scanner 3. Compact spots for Citalopram HBr were observed having Rf value of
0.46±0.02. Linear regression analysis of the data for the calibration plots showed good linear
relationship in the concentration range of 2-12mcg/spot with respect to peak area and r value was
found to be 0.9960. The method was validated as per ICH guidelines for accuracy calculated as
% recovery was in the range of 98.63% to 101.72%. The statistical analysis of the data showed
that the method is reproducible and selective for the estimation of Citalopram HBr in tablet
dosage form during routine analysis.
15
.

13. AIM:Theexistingphysicochemicalmethodsareinadequatetomeettherequirements;hence
itisproposedtoimprovetheexistingmethodsandtodevelopnewmethodsfortheassay&
stabilitystudiesofCitalopraminpharmaceuticaldosageformsadaptingdifferentavailable
analyticaltechniqueslikeUVspectrophotometryandHPLC.
OBJECTIVES:Theobjectivesoftheproposedmethodistodevelopsimpleandaccurate
methodsforthedeterminationofCitaloprambyRP-HPLCmethodinpharmaceuticaldosage
forms&it’sstabilityindicativestudies.
PLANOFWORK
1. To undertake solubility study & analytical study of Citalopram & to develop initial UV &
chromatographic conditions.
2. Optimisation of initial chromatographic conditions.
3. Analytical method validation of developed stability indicating method.
4. Quantitative determination of Citalopram in pharmaceutical dosage form using the method
developed and validated.
III. AIM, OBJECTIVES & PLAN OF WORK

14. DRUG SAMPLES
Citalopramreference standard was obtained from Hetero Labs ,Jadcherla.
FORMULATION
Celexa-10 Tablet containing 10 mg Citalopramwas obtained from local Pharmacy
CHEMICALS AND SOLVENTS
All the chemicals used were of analytical grade and Spectral grade,HPLC grade.
The chemicals used for the study were,
Doubled distilled water. Methanol HPLC grade Acetonitrile HPLC grade
Urea A.R. Grade HclA.R. Grade H
2O
2 A.R. Grade
Phosphoric acid A.R. Grade
Sodium hydroxide A.R. Grade
4.2 INSTRUMENTS
INSTRUMENTS EMPLOYED
Single beam UV-Visible Spectrophotometer (Electronics India, Model: UV2310, Software:
UV Probe)
HPLC System (Shimadzu-LC 10 AT VP ,Software: Autochro-3000)
Digital weighing balance (Sartorius, Model: CP225D)
Digital Ultrasonicator
pH Meter (ELICO, Model 113)
Micro-Pipette
IV.EXPERIMENTAL WORK

15. IV.EXPERIMENTAL WORK
Selectionofwavelength
Thestandard&samplestocksolutionswerepreparedseparatelybydissolvingstandard
&sampleinaUreaanddilutedwithAcetonitrileforUVanalysisforthefinal
concentration10µg/ml.WhilescanningtheCitalopramsolutionweobservedthe
absorptionmaximawas239nm.ThescannedUVspectrumisattachedinFigure.
UV spectrum of Citalopram

16. IV.EXPERIMENTAL WORK
HPLCMETHODDEVELOPMENT TRAILS
Preparation of standard solution of Citalopram
25 mg of Citalopram was weighed accurately and transferred into 25 ml volumetric flask. About 10 ml of
mobile phase was added and sonicated to dissolve. The volume was made up to the mark with same solvent.
The final solution contained about 1000 μg/ml of Citalopram. From the stock solution again 0.1 ml was taken
in a 10 ml volumetric flask & volume was make up to the mark by mobile phase. This solution contains 10
μg/ml of Citalopram which has been injected to HPLC.
Initialization of the instrument
The HPLC instrument was switched on. The column was washed with HPLC water for 45 minutes. The
column was then saturated with mobile phase for 45 minute. The mobile phase was run to find the peaks.
After 20 minutes the standard drug solution was injected in HPLC.
Different chromatographic conditions used and their Optimizations
The different HPLC chromatographic conditions were used to find out the optimum chromatographic
condition for best elution of drugs.
CHROMATOGRAPHIC CONDITIONS:
Instrumentused :ShimadzuHPLCwithmanualinjectorandUVdetector
Injectionvolume :10µl
Runtime :10min

17. Mobilephase Water:ACN(70:10)
Wavelength 239nm
Flowrate 0.8ml/min.
Runtime 10min.
Column HiqSil,C-18,Vsize(250mm*4.6mm)0.41
012345678910
Retention Time (min)
0
1
2
3
4
5
Intensity (mV)
Chromatographic Trials
Mobilephase Water:Methanol(40:60)
Wavelength 239nm
Flowrate 0.8ml/min.
Runtime 10min.
Column HiqSil,C-18,Vsize(250mm*4.6mm)2.78
3.09
3.73
4.69
5.29
7.69
8.27
012345678910
Retention Time (min)
0
1
2
3
4
Intensity (mV)
Mobilephase Water:Methanol(40:60)
Wavelength 239nm
Flowrate 1.0ml/min.
Runtime 10min.
Column DevelosilODSHG-5RPC
18,5m,
15cmx4.6mmi.d.

18. Mobilephase Water:Methanol(70:30)
Wavelength 239nm
Flowrate 1.0ml/min.
Runtime 10min.
Column DevelosilODSHG-5RPC
18,5m,
15cmx4.6mmi.d.2.87
3.57
4.90
7.91
012345678910
Retention Time (min)
0
1
2
3
4
5
Intensity (mV)
Mobilephase Potassiumdihydrogenphosphatebuffer:Methanol
(20:80)
Wavelength 239nm
Flowrate 0.8ml/min.
Runtime 20min.
Column DevelosilODSHG-5RPC
18,5m,15cmx4.6mm
i.d.4.45 7.39
8.87
16.14
02468101214161820
Retention Time (min)
0
5
10
15
20
Intensity (mV)
Mobilephase phosphatebuffer(pH3.0):ACN(80:20)
Wavelength 239nm
Flowrate 1.0ml/min.
Runtime 10min.
Column DevelosilODSHG-5RPC
18,5m,
15cmx4.6mmi.d.1.65
1.91
7.42
012345678910
Retention Time (min)
0
20
40
60
80
Intensity (mV)
Optimized Method Chromatogram of Citalopram (Rt 1.91)

19. Stresscondition Time Assayofactive
substance
Assayofdegraded
products
MassBalance
(%)
AcidHydrolysis(0.1MHCl) 24Hrs.28.12 78.2 98.56
BasicHydrolysis(0.IMNaOH)24Hrs.45.36 55.02 98.49
ThermalDegradation(50
0
C)24Hrs.98.39 ----------- 98.31
UV(254nm) 24Hrs.81.26 29.64 98.53
3%Hydrogenperoxide 24Hrs.79.15 25.42 98.03
FORCEDDEGRADATION STUDIES:
TheAPI(Citalopram)wassubjectedtostressTrialinvariouswaystoobservetherate
andextentofdegradationthatislikelytooccurinthecourseofstorageand/orafter
administrationtobody.Thisisonetypeofacceleratedstabilitystudiesthathelpsus
determiningthefateofthedrugthatislikelytohappenafteralongtimestorage,
withinaveryshorttimeascomparetotherealtimeorlongtermstabilitytesting.The
variousdegradationpathwaysstudiedareacidhydrolysis,basichydrolysis,thermal
degradationandoxidativedegradation.
Theresultsofthestressstudiesindicatedthespecificityofthemethodthathasbeen
developed.Theresultofforceddegradationstudiesaregiveninthefollowingtable.
Results of force degradation studies of Citalopram API.

20. 1.47
1.66
1.94
3.16
5.74
0 1 2 3 4 5 6 7
Retention Time (min)
0
2
4
6
8
10
12
14
Intensity (mV) ACIDHYDROLYSIS1.64
1.91
3.77
0 1 2 3 4 5 6 7
Retention Time (min)
0
20
40
60
80
Intensity (mV)
BASIC HYDROLYSIS1.64
1.91
3.79
0 1 2 3 4 5 6 7
Retention Time (min)
0
20
40
60
80
Intensity (mV)
THERMAL DEGRADATION PHOTOLYTIC DEGRADATION
OXIDATION with (3%) H
2O
2
FORCEDDEGRADATION STUDIES:

21. LinearityandRange:
Linearityrangewasfoundtobe5-20µg/mlfor
Citalopram.Thecorrelationcoefficientwas
foundtobe0.999,theslopewasfoundtobe
47542andinterceptwasfoundtobe11245for
Citalopram.
MethodValidation
Accuracy-Recoverystudy:
Todeterminetheaccuracyoftheproposed
method,recoverystudieswerecarriedoutby
addingdifferentamounts(80%,100%,and
120%)ofpuredrugofCitalopramweretaken
andaddedtothepre-analyzedformulationof
concentration10g/ml.Fromthatpercentage
recoveryvalueswerecalculated.Theresults
wereshownintable.
Sample ID
Concentration (µg/ml) %Recovery of
Statistical Analysis
Pure
drug Formulation Pure drug
S1 : 80 % 8 10
102.41
Mean= 101.64%
S2 : 80 % 8 10
101.27
S.D. = 0.667008
S3 : 80 % 8 10
101.24
% R.S.D.= 0.656
S4 : 100 % 10 10
99.56
Mean= 99.58%
S5 : 100 % 10 10
99.32
S.D. = 0.275741
S6 : 100 % 10 10
99.87
% R.S.D.= 0.277
S7 : 120 % 12 10
99.84
Mean= 99.65%
S8 : 120 % 12 10
99.31
S.D. = 0.297714
S9 : 120 % 12 10
99.81
% R.S.D. = 0.299

22. Conc.of
Citalopram
(API)(µg/ml)
Observed Conc. of Citalopram(µg/ml) by the proposed method
Intra-Day Inter-Day for Two days
Day-1 Day-2
Mean(n=6)%RSD Mean(n=6)%RSD Mean(n=6)%RSD
10 10.003 1.210 10.012 0.891 10.014 0.931
Precision
Intradayandinterdayprecisionstudieswereconductedbytakingfinalconcentrationof10µg/mlofstandard
andinjectedintoHPLC.ItshowsthatthemeanRSD(%)wasfoundtobewithinacceptancelimit(≤2%),so
itwasconcludedthattherewasnosignificantdifferencefortheassay,whichwastestedwithindayand
betweendays.Hence,methodatselectedwavelengthwasfoundtobeprecise.
Data for Citalopram analysis
LOD&LOQ
TheLODandLOQwerecalculatedbytheuseoftheequationsLOD=3.3×σ/SandLOQ=10×σ/S
whereσisthestandarddeviationofinterceptofCalibrationplotandSistheaverageoftheslopeofthe
correspondingCalibrationplot.TheMinimumconcentrationlevelatwhichtheanalytecanbereliable
detected(LOD)&quantified(LOQ)werefoundtobe0.416&01.324µg/mlrespectively.

23. S.No.ParameterLimit Result
1 ResolutionRs2 9.15
2 AsymmetryT2 Citalopram=0.12
3 Theoretical
plate
N2000Citalopram=3246
SystemSuitabilityParameter
Systemsuitabilitytestingisanintegralpartof
manyanalyticalprocedures.Thetestsare
basedontheconceptthattheequipment,
electronics,analyticaloperationsandsamples
tobeanalyzedconstituteanintegralsystem
thatcanbeevaluatedassuch.Following
systemsuitabilitytestparameterswere
established.ThedataareshowninTable.
Data of System Suitability Parameter
EstimationofCitalopraminTabletDosageForm
TwentytabletsweretakenandtheI.P.methodwasfollowedtodeterminetheaverageweight.Aboveweighed
tabletswerefinallypowderedandtrituratedwell.Aquantityofpowderequivalentto25mgofdrugswere
transferredto25mlvolumetricflask,makeandsolutionwassonicatedfor15minutes,thereaftervolume
wasmadeupto25mlwithsamesolvent.Then10mloftheabovesolutionwasdilutedto100mlwith
mobilephase.Thesolutionwasfilteredthroughamembranefilter(0.45m)andsonicatedtodegas.The
solutionpreparedwasinjectedinfivereplicatesintotheHPLCsystemandtheobservationswererecorded.
AduplicateinjectionofthestandardsolutionwasalsoinjectedintotheHPLCsystemandthepeakareas
wererecorded.ThedataareshowninTablesandthechromatogramobtainedisshowninfig.

24. Brand name of TabletsLabelled
amount of
Drug (mg)
Mean (SD)
amount (mg)
found by the
proposed method
(n=6)
% RSD
Celexa-10mg Tablet
{Cyril Pharmaceuticals}
10 9.82 (0.498)99.82 (0.343)
Sl. NoRt Theoretical
Plates
Area Tailing
factor
1 1.91 55673 664563 0.62
Assay Data for estimation Citalopram in Celexa-10mg tablet1.65
1.91
0 1 2 3 4 5 6 7
Retention Time (min)
0
20
40
60
80
Intensity (mV)
TheamountofdrugCelexa-10mgTabletwasfoundtobe9.82(0.343)mg/tabfor
Citalopram&%assaywas99.82.
Chromatogram for assay sample
Assaychromatogramresultsofsample

25. Todevelopaprecise,linear,specific&suitablestabilityindicatingRP-HPLCmethodforanalysisof
Citalopram,differentchromatographicconditionswereapplied&theresultsobservedarepresented.
Isocraticelutionissimple,requiresonlyonepump&flatbaselineseparationforeasyandreproducible
results.So,itwaspreferredforthecurrentstudyovergradientelution.
IncaseofRP-HPLCvariouscolumnsareavailable,buthereDevelosilODSHG-5RPC
18,5m,15cmx
4.6mmi.d.columnwaspreferredbecauseusingthiscolumnpeakshape,resolutionandabsorbancewere
good.Detectionwavelengthwasselectedafterscanningthestandardsolutionofdrugover200to400nm.
FromtheU.VspectrumofCitalopramitisevidentthatmostoftheHPLCworkcanbeaccomplishedinthe
wavelengthrangeof240-300nmconveniently.Further,aflowrateof1ml/min&aninjectionvolumeof
20µlwerefoundtobethebestanalysis.Theresultshowsthedevelopedmethodisyetanothersuitable
methodforassaywhichcanhelpintheanalysisofCitalopramindifferentformulations.
Asensitive&selectivestabilityindicatingRP-HPLCmethodhasbeendeveloped&validatedforthe
analysisofCitalopramAPI.
FurthertheproposedRP-HPLCmethodhasexcellentsensitivity,precision.Theresultshowsthedeveloped
methodisyetanothersuitablemethodforassay,puritywhichcanhelpintheanalysisofCitalopramin
differentformulations.
V.RESULTS&DISCUSSION
VI.CONCLUSION

26. VII.BIBLIOGRAPHY
1.InstrumentalMethodsofChemicalAnalysisbyB.K.Sharma,pp.75-78,113-115.
2.nstrumentalMethodsofChemicalAnalysis,VthEd.,byGalenW.Ewing,pp128-237.
3.PharmaceuticalAnalysis,Istedition,byTakeruHiguchi,EinarBrochmann,HanffenHanssen,1-10.
4.PracticalPharmaceuticalChemistry,IVedition,VolumeII,byA.H.Beckett,J.B.Stenlake,275-298.
5.QuantitativeAnalysisofdrugsinPharmaceuticalformulation,IIIrdEd.,byP.D.Sethi,pp.1-21,51-56.
6.Kastureetal,HandbookofPharmaceuticalAnalysis,Volume-1.Shetti.P.D,HighPerformanceLiquid
Chromatography,2001,P.11
7.ValidationofAnalyticalProcedures,Methodology,ICHHarmonizedTripartiteGuidelines,1996.
8.https://go.drugbank.com/drugs/DB00215-Citalopramdrugbank.
9.G.H.Ragab,E.A.Bahgat-DevelopmentofbioanalyticalHPLCmethodforsimultaneousdeterminationof
theantialzhiemer,donepezilhydrochlorideandtheantidepressant,citalopramhydrobromideinraw
materials,spikedhumanplasmaandtabletsdosageform,AnnalesPharmaceutiquesFrançaises,Volume77,
Issue2,March2019,Pages112-120
10.AmitSuryakantTapkir,ShitalMagardhwajBiradar,SwapnilArjunHajareandPravinDigambar
Chaudhari.DevelopmentandValidationofStabilityIndicatingAssayMethods(SIAMs)forCitalopramHBr
byUsingUV-VisibleSpectrophotometerandRP-HPLC.DerPharmaciaLettre,2016;8(3):7-18A

27. VII.BIBLIOGRAPHY
11.SandiriNandeshwari,Dr.KhajaZeeyauddinandYagnambhatlaRajendra-animprovedvalidatedRP-
HPLCmethodforseparationofCitalopramhbrimpuritiesincitalopramhbrtablets,ejbps,2022,Volume9,
Issue1,132-137.
12.CH.AjayKumar,A.PrabhakarReddy,G.LakshmiSuneetha,M.SaiSree,M.VijayaLakshmiandBuchi
N.Nalluri-DevelopmentandvalidationofRP-HPLC-PDAmethodfortheanalysisofCitalopram
hydrobromideinbulk,dosageformsandininvitrodissolutionsamplesJournalofChemicaland
PharmaceuticalResearch,2014,6(11):326-333
13.AsadRazaandTariqMahmoodAnsari-Spectrophotometricdeterminationofcitalopramhydrobromide
intabletdosageformusingchloranilPak.J.Pharm.Sci.,Vol.27,No.2,March2014,pp.255-260.
14.K.Sujatha,Bj.V.L.N.SeshagiriRao-ANewValidatedRp-HplcMethodForTheEstimationOf
CitalopramInTabletDosageFormsAnInternationalJournalofAdvancesinPharmaceuticalSciences,
Volume4,Issue6,November-December2013,Pages1299-1306.
15.C.Saravanan,M.Thamizhmozhi,C.A.SureshKumar,C.Sudhakar,BandaruRajesh,G.SenthilKumar-A
NovelAndRapidHptlcMethodForTheAnalysisofCitalopramHydrobromideInTabletDosageForm–
DevelopmentAndValidation-JournalofAdvancedScientificResearch,2012,3(1):62-64.