ERRORS- Introduction and classification-

Error-Introduction and classification

1. 2. ERRORS
Presented By-
Mr. Dattatraya B Thorat
M. Pharm.
Head of Department
PRES, Institute of Pharmacy, Loni

2. SOURCES AND TYPES OF ERRORS-
Errors-Theexperimentalvaluediffersfromtheactualvalueeven
thoughrepeatedexperimentscanfailedtogiveidenticalresults.Such
discrepanciesintheresultsareduetovarioussourcesoferrors.
A.DeterminateErrors:(Systematicerrors/constanterrors)
These are also called as systematic errors.
1.Personal error-may be by the individual analyst.
E.g-a. poorely judged visual end points due to colorblindness or due
to late reading of end points b. mathematical errors in calculation.
2.Errors in method-caused by incorrect procedure.
e.g-incorrect sampling, contamination of precipitates
3.Instrumental or apparatus errors-due to poor construction or
calibration.
e.g.-incorrect weights, poorly calibrated flasks, burettes, pipettes.
4.Chemical error -due to impurities in chemicals solvents and
reagents.
Errors of above categories are usually detectable and can be
eliminated to the large extent.

3. B. Indeterminate Errors ( Accidental
errors/Random error)
PRECISION AND ACCURACY-
Inpharmaceuticalanalysis,ultimateresultofanalysisisimportant
fromaccuracyandreliabilitypointofview.
The term accuracy is the difference between true value and value of
experimental result. An experimental procedure may be highly
precise ,but because of some errors the results could be inaccurate.
Precisionisthevariabilityamongreplicateamongreplicate
measurementsi.e.howclosethevaluesofresultsofreplicate
measurementsaretoeachother.Itisdegreeofagreementbetween
variousresultsofthesamequantitythatisthereproducibilityofa
result.

4. SIGNIFICANT FIGURES
Inotherwordssignificantfiguresarethedigitsthatareplaced
inordertogivethevaluetoanumbere.ginthequantityrepresented
bythenumber346thedigits3,4,6aresignificantfigures.Zeroisthe
significantfigureinsomecases,whileinothercaseswhereitisused
tolocatethedecimalpointzeroisnotconsideredassignificantfigure.
Innumber30.6,thezeroissignificantfigurebutinthenumber
0.0235,thezerobeforethepointisnotsignificantbutshowstheorder
ofmagnitudeofotherdigits.
Iftheweightofthecompoundisexpressedas2.0001gm,thezeros
aresignificantbecausetheyindicatethattheweighinghasbeenmade
to0.0001gm.

7. ImpuritiesinPharmaceuticals-
Impurityistheundesirableforeignmaterialwhichmaybetoxicor
maynotbetoxicpresentinpharmaceuticalpreparation.
meanspresenceofothermaterialsthandrugorpresenceof
unwantedforeignparticleotherthanactivedrugs.Theimpurities
maybetoxicornon-toxicevenifitisnon-toxicitmaybeused
intentionallyasadulteranttoincreasetheweightoftheactive
ingredient.Nontoxicimpuritiesalsoreducetheactivityofthedrug,
sothatonemustavoidimpuritiesinpharmaceuticals,cannot
eliminatealltheimpurities.Theofficialpharmacopoeiasprescribe
limitsforparticularimpuritieslikesulphate,chloride,iron,heavy
metalsandarsenic.

8. SOURCESOFIMPURITIES
1)Rawmaterialsusedinthemanufacture2)Processesusedinthe
manufacture
3)Intermediateproductsinmanufacturingprocess4)Defectsin
manufacturingprocess/manufacturinghazards5)Solvents6)
Actionofsolventandreagentsonreactionvessel
7)Materialoftheplant
8)Inadequatestorage:
a)Filth
b)Decompositionoftheproductduringstorage
9)Accidentalsubstitutionordeliberateadulterationwithspurious
oruselesssubstances
10)Manufacturinghazards:
i)Particulatecontamination ii)Processerrors
iii)Crosscontamination ivMicrobialcontamination
v)Packingerrors

9. 1.RawMaterials-Whensubstancesorchemicalsaremanufactured;
therawmaterialsfromwhichthesearepreparedmaycontain
impuritieswhichgetincorporatedintofinalproduct.Example-sodium
chloridepreparedfromrocksaltcontainstracesofCalcium&
Magnesiumcompounds.
2.Reagentsusedinmanufacturingprocess:Synthesisofdrugs
involvesmanychemicalreactionslikenitration,halogenation,
oxidationandhydrolysis.Thesereactionproductsthenoccuras
impuritiesinthefinalproduct.Thusimpuritiesofiron,lead,andheavy
metals,copperareduetotheabovementionedreasons.
3.Defectsinthemanufacturingprocess:Defectssuchasimperfect
mixing,incompletenessofreaction,non-adherencetoproper
temperature,pressure,pHorreactionconditionetc.mayresultinthe
productionofchemicalcompoundswithimpuritiesinthem.
4.Storagecondition-Thechemicalwhenpreparedisstoredin
differenttypesofcontainers.Varioustypesofmaterialsareusedfor
storagepurpose.Thereactionmaytakeplacedirectlyorleachingout
effectonthestoragevessel.Thisactsasimpurity.Also,rodents&
insectsmayaddimpuritiestotheproducts.

10. 5.Solvents:Wateristhesolventeasilyavailable&cheapandisused
inthemanufactureofinorganicchemicals.Thiscangiverisetotrace
impuritiessuchassodium,calcium,magnesium,carbonate&
sulphateions.
6.Decomposition-Decompositioniscausedbylight,air,oxygen&
causescontaminationoffinalproduct.Anumberoforganic
substancesgetspoiledbecauseofdecompositiononexposuretothe
atmosphere.E.g.amines,phenol,potentdrugs.
7.Atmosphericcontaminants:Atmosphericcontaminationmaytake
placethroughdust,sulphurdioxide,hydrogensulphide&arsenic.
Carbondioxide&watervapourarepossiblecontaminantsof
substanceswhichareaffectedbytheiraction.

11. 8.ManufacturingHazards–
a)Particulatecontamination–accidentalinclusionofdirt,glass,
porcelain,Metallicorplasticfragmentfromsieves,granulating,
tabletingandfillingmachinesorevenfromproductcontainersmay
occur.
b)Processerror–Grosserrorsduetoincompletemixinginliquid
preparationsmustbedetectedbynormalanalyticalprocedures.
c)Crosscontamination–thehandlingofpowders,granulesand
tabletsinlargequantitycreateconsiderableamountofairbornedust
andmayleadtocross
contamination.
d)Microbialcontamination–liquidpreparationsandcreamsfor
topicalapplicationarepronetobacterial,fungalandmould
contamination.Specialcareshouldbetakeninparenteraland
ophthalmicpreparationtoavoidmicrobialcontamination.
9)Packagingerrors–productsofsimilarappearanceastabletsof
samesize,colorandshapepackedinsimilarcontainersmayleadto
mislabeling.

12. EFFECT OF IMPURITIES IN PHARMACEUTICAL SUBSTANCE
1.Impuritieswhicharenon-toxicbutwhicharepresentbeyondthe
limitinpharmaceuticalpreparationlowerstheactivestrengthofthat
prep.
e.g.-Impuritiesofsodiumsaltspresentinpotassiumsalt.
2.Theimpuritieswhichproducetoxiceffectonproductifpresent
beyondtheprescribedlimit.
3.Impuritiesifpresentbeyondthelimitaffectstoragecapacityof
pharmaceuticals.
e.g.presenceofmoisture.
4.Impuritiescausingtechnicaldifficultieswhileusingthesubstancein
whichitispresent.
e.g-presenceofcarbonateimpuritiesinammoniasolution.
5.Impuritiessuchascolor,odor,tasteorappearancewhichareeasily
detectablebythesenses.
e.g.Phenolicimpuritiespresentinsodiumsalicylatealtersthecolor.

13. Tests for purity-
Pharmacopoeiasprescribestestsforpurityforthe
substanceinordertoensuretheirfreedomfromthe
undesirableimpurities.
Followingtestsarethetestsforpurity-
1.Color and odor 2.Physical constants 3.Anions
4.Cations 5.Ash value
6.LOD (Loss on drying) 7.Loss on ignition 8.Humidity
9.Acidity alkalinity
10.Organic impurities 11.Arsenic or lead

14. 1.Colorandodour-
Thetestsforcolorandodouremployedonlywhenothertestfor
purityarenotapplicable.
2.Physicalconstants-
M.P,B.P,Opticalrotationetc.arephysicalconstants.
Theextentofvariationdependsonthenatureandamountof
impurities.
Determinationofphysicalconstantensureswhetherthesubstanceis
freefromimpuritiesornot.
3.Anions
AcidslikeHClorH2SO4arewidelyusedinthemanufactureof
medicinalsubstancesthereforechlorideandsulphateionsare
commonlypresentasimpuritiesinmanyofthemedicinalsubstances.
Hencetestsforanionslikechlorideandsulphateareprescribedin
officialbooks.
4.Cations-
Testsforcationsincludestestsforsodium,potassium,ammonium
radicalsandforheavymetalslikelead,ferrous,copper,etc.

15. 5.Arsenicorlead-
Boththisimpuritiesaretoxicinnaturehencetheirpresencein
medicinalcompoundsiscontrolledbyperformingthelimittestfor
arsenicandlead.
6.Insolubleconstituents-
Thecompoundwhichissolubleinwatergivesaturbidsolutionif
insolublematterispresent.
Theturbidityisduetoinsolublematerialorconstituentpresentin
watersolublecompound.
7.Organicimpurities-
Organicimpuritiesmaybefromrawmaterialorintermediately
productorbyproductsinthereaction.
8.Humidity-
The amount of moisture in the atmosphere is called humidity.
Moisture content of medicinal substances is determined to
estimate content of water of crystallization if present in the
compound.

17. 9.Acidity and alkalinity-
Excess of acidity and alkalinity has effect on keeping quality of the
compound as well as compounds with which they may mixed.
10. Ash Value-
Theresidueremainingafterincinerationistheashcontentofthat
drugwhichrepresentstheinorganicsaltsnaturallyoccurringinthe
drug.
Determinationoftheashvalueisperformedtohaveideaaboutthe
contentofforeignheavymetalsandcations.
11.LossonDrying-
Inthistestabsorbedwaterorwaterofhydrationisdeterminedby
dryingunderspecifiedcondition.
Lossonweightduetodryingalsorepresentsvolatileconstituents
includingorganicsolventsaswellaswater.
12.LossonIgnition-
Thistypeoftestisappliedtostablesubstanceswhichareliableto
containthermolabileimpurities.

18. Limittests:-
Limittestsarequantitativeorsemi-quantitativetestsdesignedto
identifyandcontrolsmallquantitiesofimpuritywhicharelikelytobe
presentinthesubstance.
IMPORTANCEOFLIMITTEST-
1.Useofthesubstanceforwhichthelimittestofimpuritiesistobe
fixed.
2.Minimumquantitiesofimpuritieslikelytobeharmfulortocause
undesirableresultsindispensingandinkeepingqualities(storage).
3.Practibalityofgettingthelimitorparticularstandardofpurity.
4.Harmfulnesoftheimpurity.

19. Discuss Arsenic Limit Test IP along with the apparatus used and
reactions involved.
Limit Test for Arsenic :
•Arsenicisanundesirableandharmfulimpurityinmedicinal
substances,andallPharmacopoeiasprescribealimittestforit.
•ThePharmacopoeialmethodisbasedontheGutzeittest.
•Whenthesampleisdissolvedinacid,thearsenicpresentinthe
sampleisconvertedtoarsenicacid.
•Thearsenicacidisreduced,byreducingagents(likepotassium
iodide,stannatedacid,etc.)toarseniousacid.
•Thenascenthydrogenproducedduringthereaction,further
reducesarseniousacidtoarsine(AsH3gas),whichreactswith
mercuricchloridepaper,producingayellowstain.
•Theintensityofthestainisproportionaltotheamountofarsenic
present.
•Astandardstainproducedfromadefiniteamountofarsenic,is
usedforcomparison

24. Explaintheprincipleinvolvedinlimittestforironwithreactions.
Principle:Limittestforirondependsupontheinteractionof
thioglycolicacidwithironinthepresenceofcitricacidandinthe
ammonicalalkalinemedium.Thisresultsintheformationof
purplecolouredferrousthioglycolatecomplex.Thelimittestof
ironiscarriedoutintwoNessler’sCylinders,onefortheTestand
otherforstandard.Theintensityofpurplecolourproducedinthe
twoiscomparedbyviewingverticallydownwards.
1.Ironimpuritymaybepresentintrivalentferricformorinthe
divalentferrousform.Ifitisinferricform,thioglycolicacid
reducesferricformofimpurityintoferrousform.
2.Itproducespurplecolouredferrousthioglycolatecomplexby
actingascomplexingagent.
RoleofCitricacid-Itpreventprecipitationofiron(ferrous)with
ammoniabyforming
ammoniumcitratebuffer.
RoleofAmmonia-Tomaintainalkalinecondition.

27. Explaintheimportanceofuseofthefollowingreagents:-
i)ThioglycollicacidinironlimittestIP.
Thioglycolicacidactsasareducingagentandreducesferricionimpurity(ifany)to
ferrousion&thenactsasacomplexingagenttoformapurplecoloredferrous
thioglycolatecomplexbyreactingwithferrousion.
ii)BariumchlorideinsulphatelimittestIP.
BariumchloridereactswithsulphateinpresenceofdiluteHCltoformbarium
sulphateprecipitate.Theturbidityoftestsolutioniscomparedwiththestandard
solution.
iii)MercuricchloridePaperinArseniclimittestIP.
IntheArseniclimittestIP,Arsinegasreactswithmercuricchloridepaperto
produceyellowstainofmercuricarsenide.Thestainoftestiscomparedwith
standardstain.
iv.Roleofleadacetatecottonplug:-
Leadacetatecottonplugisusedtotrapanyhydrogensulphidewhichmaybe
evolvedalongwitharsinegas..Itpreventstheinteractionofhydrogensulphidegas
andmercuricchloridepaper.
RoleofThioglycolicacid-
1.Ironimpuritymaybepresentintrivalentferricformorinthedivalentferrous
form.Ifitisinferricform,thioglycolicacidconvertferricformofimpurityinto
ferrousformandthenformsferrousthioglycolatecomplex.
RoleofCitricacid:Itpreventstheprecipitationofironinpresenceofammonia
RoleofAmmonia:ItmaintainsalkalinepHfortheformationofstablepurple
coloredferrousthioglycolatecomplex.

28. Explain the reaction and principle behind limit test for chloride.
The principle for limit test for chloride is based upon the measurement of opalescence
or turbidity produced in the known amount of substance (by addition of precipitating
reagent), and comparing it with the standard opalescence or turbidity.
• The limit test for chlorides is based upon the chemical reaction between soluble
chloride ions with silver nitrate reagent in a nitric acid media.
• The insoluble silver chloride renders the test solution turbid (depending upon the
amount of silver chloride formed and therefore on the amount of chloride present in
the
substance under test).
• This opalescence is compared with the standard opalescence produced by the
addition of silver nitrate, to the known amount of chloride ion (sodium chloride)
solution.
• If the test solution shows less opalescence than the standard the sample complies
the test.
Cl

30. Explain the principle along with reactions involved in limit test for sulphate I.P
Principle-
This is based upon the interaction of sulphate with barium chloride in presence
of dilute
hydrochloric acid. This results in the precipitation of sulphate as barium
sulphate.
Hydrochloric acid is added to prevent precipitation of other acid radicals.
Alcohol prevents super saturation & potassium sulphate increases sensitivity of
the test when very small quantity of sulphate ions is present. Barium sulphate
appears as turbidity.
This is compared with standard turbidity. If turbidity produced in test sample is
less than standard, it means
sample passes test.
Chemical Reaction—

32. LIMIT TEST OF HEAVY METALS

34. THANK YOU....