INTRODUCTION TO PHARMACEUTICAL CHEMISTRY AND LIMIT TEST

INTRODUCTION TO PHARMACEUTICAL CHEMISTRY, INTRODUCTION TO LIMIT TESTS, LIMIT TEST OF IRON, CHLORIDE, SULPHATE, ARSENIC AND THERE DIAGRAMS WITHTHE PRINCIPAL AND PROCEDURE OF ALL THE LIMIT TEST WITH THEIR RESULTS

1. TOPIC
INTRODUCTION TO PHARMACEUTICAL
CHEMISTRY
and Limit tests
BY
MRS. SUJATA WANKHEDE
LECTURER
NAGPUR COLLEGE OF PHARMACY,
WANADONGRI, HINGNA ROAD, NAGPUR.
MAHARASHTRA

2. Que. 1: Define Pharmaceutical Chemistry
Ans:Thechemistrywhichstudiesaboutthedrugdesignandsynthesisof
biologicallyactivemoleculesisknownasPharmaceuticalChemistry.
Theaimistoobtainnewchemicalmoleculesthatcouldenablethe
discoveryofnewpharmaceuticalsorenhancealreadyknowndrug
structures,sothattoexpandtheselectionofchemicaldrugs.
Que. 2: Explain 1) Limit tests and 2) Significant figures
Ans:
i)Limittests:Limittestsarequantitativeorsemi-quantitativetests
designedtoidentifyandcontrolsmallquantitiesofimpuritywhichare
likelytobepresentinthesubstance.
ii)Significantfigures:Thenumberofsignificantfiguresisthenumber
ofdigitswhicharenecessarytoexpressresultswhichareconsistentwith
theprecisionofthemeasurement.

3. Que.3:ExplaintheprincipleandreactioninvolvedinIronlimittestI.P.
Ans:Principle:Limittestforirondependsupontheinteractionofthioglycolic
acidwithironinthepresenceofcitricacidandintheammonicalalkaline
medium.Thisresultsintheformationofpurplecoloredferroussaltsof
thioglycolicacid.ThelimittestofironiscarriedoutintwoNessler’sCylinders,
oneforthe‘test’andotherfor‘standard’.Theintensityofpurplecolor
producedinthetwoiscomparedbyviewingtransversely.Ifthecolorintensity
oftestsolutionislessthanthatofstandard,thesamplepassesthetest&Ifthe
intensityofcolourismoreinthetestsamplethaninthestandard,itmeansthat
thesamplecontainsmorequantityofironimpuritythanthepermissiblelimit
andhencesampleisdeclaredasnotofstandardquality.
ChemicalReaction:

4. RoleofThioglycolicacid-
Ironimpuritymaybepresentintrivalentferricformorinthedivalent
ferrousform.Ifitisinferricform,thioglycolicacidconvertferricform
ofimpurityintoferrousformandthenformsferrousthioglycolate
complex.
RoleofCitricacid:Itpreventstheprecipitationofironinpresenceof
ammonia
RoleofAmmonia:ItmaintainsalkalinepHfortheformationofstable
purplecoloredferrousthioglycolatecomplex.

5. Que. 4: Give procedure involved in the limit test in iron.
Ans: Procedure:
2)Add2mlofa20%w/vCitricAcidironfreesolutiontoboth.
3)Add0.1mlofthioglycollicacidtobothmixwell&makealkalinewith
ironfreeammoniasolution.
4)Diluteto50mlwithdistilledwater&allowtostandfor5minutes.
5)Comparetheintensityofcolourproducedinthetestsolutionwiththe
standard.
6)Reportaccordingly.
Standard Solution Test Solution
1)Pipetteout2.0mlofiron
standardsolutioninalabeled
Nessler’sCylinder&add20mlof
distilledwater.
1)Weigh2gmofgivensample&
dissolveIn20mlofdistilledwater
inalabeledNessler’sCylinder.

6. Que.5:Explaintheprinciplealongwithreactionsinvolvedinlimit
testforsulphateI.P
Ans:Principle:Thisisbasedupontheinteractionofsulphatewith
bariumchlorideinpresenceofdilutehydrochloricacid.Thisresultsin
theprecipitationofsulphateasbariumsulphate.Hydrochloricacidis
addedtopreventprecipitationofotheracidradicals.Alcoholprevents
supersaturation&potassiumsulphateincreasessensitivityofthetest
whenverysmallquantityofsulphateionsispresent.Bariumsulphate
appearsasturbidity.Thisiscomparedwithstandardturbidity.Ifturbidity
producedintestsampleislessthanstandard,itmeanssamplepassestest.
ChemicalReaction:
BaCl2+SO4 BaSO4+2Cl

7. Que. 6: Procedure for Limit test for sulphateIP
Ans:
Standard Solution Test Solution
1.Take1mlof25%w/vofbariumchloride
inNesseler’sCylinder.
1.Take1mlof25%w/vofbariumchloride
inNesseler’sCylinder.
2.Add1.5mlofethanolicsulphatestandard
solution(10ppmSO4--)mixandallowto
standfor1min.
2.Weighonegramofsample(Sodium
Bicarbonate)andaddtolabeledNessler’s
cylinder.
3.Add0.15mlof5Maceticacidin
Nesseler’scylinder
3.Add1.5mlofethanolicsulphatestandard
solution(10ppmSO4--)mixandallowto
standfor1min.
4.Diluteupto50mlwithwaterandstirwith
glassrod
4.Add10mldistilledwaterand
neutralizewithhydrochloricacidandadd15
mlofdistilledwater.
5.Allowtostandfor5min 5.Add0.15mlof5Maceticacidin
Nesseler’scylinder
6..Diluteupto50mlwithwaterandstir
with
glassrodandallowtostandfor5min.

8. Que.7:GivetheprincipleandreactionsinvolvedinLimitTestfor
Chloride(I.P.)
Ans:Principle:Limittestforchloridesdependupontheinteractionof
chlorideswithsilvernitrateinthepresenceofnitricacid.Thisresultsin
theprecipitationofSilverchloride.Whenonlyverysmallquantityof
chlorideionsarepresent,silverchlorideappearsasopalescenceandnot
asprecipitate.Silverchlorideappearsasopalescencewhichiscompared
withstandardinNesslercylinder.Thestandardturbidityisproducedby
theactionofsilvernitratesolutionwith1mlof0.05845%w/wof
Sodiumchloride(ChlorideStandardSolution-25ppmCl).
Nitricacidisaddedtopreventprecipitationofotheracidradicalssuchas
phosphate,sulphateetc.withsilvernitratesolution.
Reaction:
Cl-+ AgNO3 AgCl↓ + NO3 –
NaCl+ AgNO3 AgCl↓ + NaNO3

9. Que. 8: Procedure involved in Limit Test for Chloride (I. P.)
Ans: Procedure:
2.Add10mlofdiluteNitricacid.
3.Diluteto50mlmarkwithdistilledwater.
4.Add1mlof0.1MsolutionofSilvernitrate.
5.Stireachsolutionwithglassrodandallowtostandfor5minutes&
comparetheopalescencetransverselyagainstadarkbackground.
Test Standard
1.Dissolve1gmofsamplein
about10mlofdistilledwaterand
transferittoaNesslercylinder
labeledas‘Test’.
1.Place10mlofChloride
Standardsolution(25ppmCl)in
NesslerCylinderlabeledas‘
Standard’.

10. Que.9:Explaintheprincipleandreactionsinvolvedinlimittestfor
arsenicalongwithwelllabeleddiagramofapparatususedinit.
Ans:Principal:
Step-1
Limittestforarsenicisbasedonsemiquantitativedeterminationof
arsenicimpuritiesinthetestsampleofdrug.Thesampleisdissolvedin
stannatedacidwhichconvertsthearsenicimpuritiestoarseniousacidor
arsenicaciddependinguponvalencystateofarsenicimpuritypresentin
thetestsample.

11. Step-2
Whenacidicsolutionofsampletreatedwithreducingagent(Stannous
chloride)convertspentavalentarsenicacidintotrivalentarseniousacid.
Step-3
Step-4
Thearseniousacidisthenconvertedintogaseoushydride(Arsinegas)
withthehelpofnascenthydrogenwhichisproducedbyZincand
hydrochloricacid.

12. Step -5
Arsinegasiscarriedthroughthetubebythesteamof
hydrogenandoutthroughthemercuricchloridepaper.A
reactionoccursbetweenarsineandmercuricchloride,which
produceyellowcolourstain.
Step-6
Thestainproducedbytestsamplecomparedwiththatof
standardarsenicsolution.Thelimitofarsenicisexpressedas
partpermillion.

13. Diagram: Gutzeitapparatus

14. Que.10:Explaintheroleofleadacetatecottonplugandmercuric
chloridepaperinarseniclimittest.
Ans:
Roleofleadacetatecottonplug:
Leadacetatecottonplugisusedtotrapanyhydrogensulphidewhich
maybeevolvedalongwitharsinegas.Itpreventstheinteractionof
hydrogensulphidegasandmercuricchloridepaper.
RoleofMercuricchloridepaper:
Conversionofarseniousacidtoarsinegaswhichreactswithmercuric
chloridepapergivesyellowstain;depthofyellowstainonmercuric
chloridepaperwilldependuponquantityof
arsenicpresentinthesample.

15. Que.11:Definethetermimpurity.Explainvarioussourcesof
impuritiespresentinpharmaceuticals.
Ans:Definition:Itistheundesirableforeignmaterialwhichmaybe
toxicormaynotbetoxic,presentinthepharmaceuticalsubstances.
Impurityisthesubstanceorthematterwhichdoesnotformpartofthe
medicinalorpharmaceuticalsubstancesordrugs.
SourcesofImpurities:
1.Rawmaterial
2.Reagentsusedinmanufacturingprocess
3.Intermediateproductsinmanufacturingprocess
4.Defectsinmanufacturingprocess/manufacturinghazards
5.Solvents
6.Actionofsolventandreagentsonreactionvessel
7.Atmosphericcontaminationduringmanufacturingprocess
8.Defectivestorageoffinalproducts
9.Adulteration

16. 1.RawMaterials:Whensubstancesorchemicalsare
manufactured;therawmaterialsfromwhichtheseare
preparedmaycontainimpuritieswhichgetincorporated
intofinalproduct.Example-sodiumchlorideprepared
fromrocksaltcontainstracesofCa&Mgcompounds.
2.Reagentsusedinmanufacturingprocess:Synthesisof
drugsinvolvesmanychemicalreactionslikenitration,
halogenation,oxidationandhydrolysis.Differentchemicals&
solventsareusedinthesechemicalprocesses.Whenchemical
reactionsarecarriedoutinreactionvessel,thematerialof
thesevessels(Iron,tin,copper,aluminiumetc.)isreacted
uponbythesolvents,chemicals&reactionproductsare
formed.Thesereactionproductsthenoccurasimpuritiesin
thefinalproduct.Thusimpuritiesofiron,lead,andheavy
metals,copperareduetotheabovementionedreasons.

17. 3.Defectsinthemanufacturingprocess:Defectssuchas
imperfectmixing,incompletenessofreaction,non-adherence
topropertemperature,pressure,pHorreactionconditionetc.
mayresultintheproductionofchemicalcompoundswith
impuritiesinthem.
4.Storagecondition:Thechemicalwhenpreparedisstored
indifferenttypesofcontainers.Varioustypesofmaterialsare
usedforstoragepurpose.Reactionofsubstancewithmaterial
ofthestoragevesselmaytakeplace.Thereactionmaytake
placedirectlyorleachingouteffectonthestoragevessel.This
actsasimpurity.Also,rodents&insectsmayaddimpuritiesto
theproducts.

18. 5.Solvents:Wateristhesolventeasilyavailable&cheapand
isusedinthemanufactureofinorganicchemicals.Thiscan
giverisetotraceimpuritiessuchassodium,calcium,
magnesium,carbonate&sulphateions.
6.Decomposition:Decompositioniscausedbylight,air,
oxygen&causescontaminationoffinalproduct.Anumberof
organicsubstancesgetspoiledbecauseofdecompositionon
exposuretotheatmosphere.E.g.amines,phenol,potentdrugs.
7.Atmosphericcontaminants:Atmosphericcontamination
maytakeplacethroughdust,sulphurdioxide,hydrogen
sulphide&arsenic.Carbondioxide&watervapourare
possiblecontaminantsofsubstanceswhichareaffectedby
theiraction.