Primary and secondary standards

Primary and secondary standard solution in pharmaceutical analysis

1. Primary and secondary
standards
NEELIMAYADAV
ASST. PROF.
DR C.V. RAMANINSTITUTE OF PHARMACY

2. STANDARDS:-
Thewordstandardmeansamaterialcontainingasubstanceofourinterestwithaknownconcentration.Wecan
expressthiswithdefinitenumberswithproperunits.Byusingthisstandardwecanfindouttheconcentrationof
thatsubstanceinanewmaterial.
1. Functions
standards has the following uses:-
(a) To provide a reference using which we can determine unknown concentration
(b) To standardize volumetric solutions
(c) Preparation of secondary standard
(d) To calibrate an instrument.
2. Types
Standards can be divided into two types:
1. Primary standard
2. Secondary standard

3. Primary standard and Secondary standards
Standards
Primary standards
Secondary standards

4. 1.Primarystandard:-
Fromthenameitselfitisobviousthatthisisastandardwhichcomesfirst.That’s
whythenameisprimary.
Aprimarystandardisachemicalorreagentwhichhascertainpropertiessuch
as
(a)Itisextremelypure
(b)Highlystable
(c)Itisanhydrous
(d)Itislesshygroscopic
(e)Hasveryhighmolecularweight
(f)Canbeweighedeasily
(g)Shouldbereadytouseandavailable
(h)Shouldbepreferablynontoxic
(i)Shouldnotbeexpensive
Havingsaidthatletsusunderstandeachpointonebyone.
??????Aprimarystandardmaterialshouldbeextremelypurewhichmeansthatitshouldbeachemicalof
highgradeofpurity,preferably99.98%.Inachemistrylabyouwillcomeacrosschemicalsofdifferent
gradeofpurity.Ifyoucheckthelabelyouwillnoticeanumberwithpercentagetermedaspurity.Sowhen
achemicalhaspurityof99.98%ormoreitisasuitablematerialtobeconsideredforprimarystandard.

5. UsuallythosechemicalsthatexceedtherequirementofAmericanchemicalsociety(ACS)areextremelypureand
canbeusedformakingprimarystandard.Itisananalyticalreagentofextremepuritywhichisspecially
manufacturedforthepurposeofbeingusedasprimarystandard.
??????Itshouldbehighlystablewhichmeansitusuallydoesnotreacteasilywhenkeptinitspureform.Orinother
wordsitshouldhaveverylowreactivity.Thisisimportantbecauseifareagentreactseasilywithatmospheric
oxygenorwaterorchangesitspropertyovertimethenitisunreliable.Wecanneverusesuchunstableand
unreliablechemicalsasstandard.
??????Justbeinganhydrousisnotsufficient.Thechemicalpreferablyshouldbelesshygroscopicthatisonopening
thecontaineritshouldnotabsorbwatermoleculesfromatmosphere.Whywatershouldnotenterintochemical?
Thiswillbeclearerinthefollowingpointwhereitisexplainedhowpresenceofwatermoleculecanaffectthe
simplecalculationofstandardconcentrationmakingtheentirestandardizationprocedureunreliable.

6. ??????Itcanbeweighedeasilybecauseitissopurethatitsweightisinfactatruerepresentativeofnumber
ofmolespresentinitsactualweight.
??????Oneoftheusesofprimarystandardistostandardizeavolumetricsolution.Thatmeanstheyare
usedforstandardizationoftitrationofsolutions.Itcanbeusedfortitrationofacidsaswellasbases.Let
usseehowaprimarystandardisusedfortitration.
??????Theprimarystandardisusedforcalibrationofsecondarystandardorformethodvalidationagainst
adefinitivemethodanditcorrespondstothetruevalueofthesubstanceanalyzed.

7. 2.Secondarystandard
Asecondarystandardisasubstancewhichmaybeusedforstandardizations,andwhosecontentoftheactive
substancehasbeenfoundbycomparisonagainstaprimarystandard.Asecondarystandardisasolutionwhich
containexactlyknownamountofthesubstanceinunitvolumeofthesolutionandwhichisexpressedasnormality
ormolarityandcanbedeterminedbytitratingagainstaprimarystandard.Itfollowsthatasecondarystandard
solutionisasolutioninwhichtheconcentrationofdissolvedsolutehasnotbeendeterminedfromtheweightof
thecompounddissolvedbutbyreaction(titration)ofavolumeofaprimarystandardsolution.Thusasolutionof
sodiumhydroxidemaybestandardizedbytitratingagainstastandardsolutionofPotassiumHydrogenPhthalate
oragainstastandardsolutionofHydrochloricAcid(Secondarystandard).
??????Thereareotherpointsonehastoremember.Forpreparingthesecondarystandardsolutiononemustuse
aqueoussolutionofhighgradepurity.Itmustbedeionizedifaqueoussolventusediswater.Withoutpuresolvent,
thestandardsolutionpreparedwillbeworthless(Thesepointsarealsoapplicableforpreparingprimarystandard
solution).

8. ??????Similarlybeforeusinghighgradechemicalsoneshouldalsobevigilantandcheckfordateof
manufacture,expirydate,dateofreceiptofchemical,whethertheconditionsforitstransportwas
followedornot,ifthesealisnottamperedwith,itspurity,standardreferencematerialusedetc.
Asecondarystandardisasubstancewhichforoneormoreofthereasonscannotbeusedasastandard.
e.g.,sodiumhydroxidecannotbeusedasaprimarystandardforthereasonthatitabsorbswaterand
carbondioxidefromtheatmosphereandthecompositionofitssolutionissubjecttowidevariationsat
differentperiods.SimilarlySodiumthiosulphateabsorbsCO2fromtheatmosphereandgets
decomposed.AdepositofSulphursettlesatthebottom.Similarlythecompositionsofsolutionof
variousothersubstanceslikemineralacids,Potassiumpermanganate,Iodineetc,arealsovariableat
differenttimes.Thereforethesecannotbeusedasprimarystandards.Thenormalityormolarityof
solutionofsuchasubstancecanbefoundbytitratingagainstastandardsolutionofaprimarystandard
orinotherwordsthesolutionmaybestandardizedbytitratingagainstthestandardsolutionofa
primarystandard.

9. Asecondarystandardisachemicalorreagentwhichhascertainproperties
suchas
(a)Ithaslesspuritythanprimarystandard
(b)Lessstableandmorereactivethanprimarystandard
(c)Butitssolutionremainsstableforalongtime
(d)Titratedagainstprimarystandard
Usuallyachemicalfitforbeingastandardchemicalyetdoesnotmeetthe
requirementsofaprimarystandard
??????Thebestexampleisanhydroussodiumhydroxide(NaOH).Itisextremelyhygroscopic.Assoonas
thebottleisopenedNaOHstartsabsorbingmoisturefromatmosphereandwithinnotimeitbecomes
moist.Youcan
experimentitinyourlab.TaketheNaOHbottlenearananalyticalbalance.PlaceaPetridisandmakeits
weightaszero(byusingthetarebutton).NowopenthecontainerandplacelittleNaOHcrystalonitand
quicklynotethe
weight.Nowkeeptheglasswindowsoftheanalyticalbalanceopenforfewminutesandnoticethe
gradualincreaseinitsweightintermsofmgunits.ThisisbecausetheNaOHcrystalsabsorbwater
moleculefromair.(RemembertouseaglasscontainersuchasaPetridistoweighthechemical.Because,
NaOHisacorrosiveformetalpanelofbalance).

10. ??????Anotherexampleispotassiumpermanganate(KMnO4)veryoftenassecondarystandard.Itisagood
oxidizingagentorinotherwordsitisreactivesolessstable.Moreoftenduetoitsreactivity,itsownoxidized
productmanganeseoxide(MnO2)contaminatesthecontent.That’swhyitisunsuitableforbeingaprimary
standard.Butitcanbeusedverywellasasecondarystandard.
??????Nextquestioniswhyissecondarystandardcalledstillastandard?Thisissobecausesecondarystandard
isusedasacalibratorbysmallerlaboratoriesinvolvedinactualanalysisofunknownsamples.
Calibration is the process by which we compare the measurements by a standard or an instrument
(primary) with another standard or an instrument (secondary). By doing so, we try to eliminate any variation
or difference in measurement by the secondary standard or an instrument. The other term for calibration is
standardization.

11. RequirementsforPrimaryStandards:-
Oneoftherequirementneededforvolumetricanalysisisasubstancehavingaknownpurity.The
solutionofthissubstancecanbeemployedasatitrant.Therearefewknownsubstanceswhichcan
beusedasaprimarystandard.Therequirementsforprimarystandardsubstancesareasfollows:
APrimaryStandardshouldsatisfythefollowingrequirements
1.Itmustbeeasytoobtain,topurify,todry(preferablyat110–120°c),andtopreserveinapurestate.
(Thisrequirementisnotusuallymetbyhydratedsubstances,sinceitisdifficulttoremovesurface
moisturecompletelywithouteffectingpartialdecomposition).
2.TheSubstanceshouldbeunalteredinairduringweighing:thisconditionimpliesthatitshouldnotbe
hygroscopic,oxidizedbyair,oraffectedbycarbondioxide.Thestandardshouldmaintainanunchanged
compositionduringstorage.
3.Thesubstanceshouldbecapableofbeingtestedforimpuritiesbyqualitativeandothertestsofknown
sensitivity.(Thetotalamountofimpuritiesshouldnot,ingeneralexceed0.01-0.02percent).

12. 4.Itshouldhaveahighrelativemolecularmasssothattheweighingerrorsmaybenegligible.(Theprecisionin
weighingisordinarily0.1-0.2mg;foranaccuracyof1partin1000.itisnecessarytoemploysamplesweighingat
leastabout0.2gm).
5.Thesubstanceshouldbereadilysolubleundertheconditionsinwhichitisemployed.
6.Thereactionwiththestandardsolutionshouldbestoichiometricandpracticallyinstantaneous.Thetitration
errorshouldbenegligible,oreasytodetermineaccuratelybyexperiment.

13. Examples of Primary Standards
These are materials which, after drying under the specified conditions, are recommended for use as
primary standards in the Standardization of volumetric solutions. The following are recommended
for use as primary standards, as per the Indian-Pharmacopoeialcommittee for various titrations.
I. Acid -Base Titrations Primary Standard
1. Alkalimetry (Sodium Hydroxide) : Potassium Hydrogen Phthalate
2. Acidimetry (Hydrochloric Acid,
Sulphuric Acid) : Anhydrous Sodium Carbonate
II. Oxidation-Reduction titrations (Redox titrations)
1. Permanganometry(Potassium Permanganate) : Arsenic Trioxide, Sodium Oxalate,
Potassium
dichromate
2. Iodometry (Sodium Thiosulphate) : Potassium bromate
Potassium dichromate
Potassium iodate
3. Iodimetry (Iodine) : Arsenic trioxide

14. The base NaOH is an example of a secondary standard. Commercially available NaOH contains impurities of
NaCl, Na
2CO
3, and Na
2SO
4, and readily absorbs H
2O from the atmosphere. To determine the concentration of
NaOH in a solution, it is titrated against a primary standard weak acid, such as potassium hydrogen phthalate,
KHC
8H
4O
4.
Examples of secondary Standards:-

15. THANK YOU