01. Analisis Farmasi Anorganik

5/23/2018 01. Analisis Farmasi Anorganik

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Dr.TutusGusdinarPharmacochemistryResearchGroupSchoolofPharmacy

INSTITUTTEKNOLOGI

BANDUNG


2/31

Thes llabusGeneralaspectsofpharmaceuticalanalysis:concentrationofelectrolyteand

molecularspeciation,pHandbuffersystem,associationdissociationand

equilibriumconstant;Acidimetryalcalimetry:monoprotic,polyprotic,

amphiprotic

acid

base;

buffer

capacity;

titration

curve,

indicative

reaction,

sam le anal sis Preci itation and reci itatometr : factors that influence

precipitateformationandproperties(nucleation,crystallgrowth,aging),

colloidstabilityandproperties;titrationcurve,indicativereaction,sample

chelatecomplex,

EDTA;

titration

curve,

indicative

reaction,

sample

analysis,

Oxidimetryreductometry:redoxsystem,redoxequilibriumconstant;

cu v , c v c , y ; v c y :

gravimetricanalyticaltechniqueandseparation; Technicalapplicationon

pharmaceuticalsubstances

and

preparation:

titrimetric

typology,

titration

feasibility,calculationandresponsemeasurement,indicativereactions;

Separationandmeasurementtechniquesandanalyticalerrors:separation

techniquesandapplicationofreactionsinpharmaceuticalanalysis;statistics

andanalyticalerrors.


3/31

Metodekimiaanalisisuntukmenentukankadar

sen awa

terdiriatas

ravimetri

dan

titrimetri. Keduametodetersebut

dalamsatuan

internasional

(SI

units).

Metodeklasikdigunakanuntukmenentukan

kadardalam

ukuran

besar

(1

100%),

sedangkanuntuk ukurankadaryang


4/31

Classical analysishashadalonganddistinguishedhistory.

ecru e

c ass ca

ana yses

o

epas

ave

eenimprovedasbettervaluesforatomicmassesbecame

available,astheprinciplesofphysicalchemistrywereapp ie ,asorganic reagentswereintro uce ,an asinstrumentaltechniquesbecameavailablefortheevaluation

of

the

s stematic

errors

inherent

in

both

gravimetry andtitrimetry.

x s ng

so ope

u on

mass

spec rome ry

an

new

g

performanceinductively

coupled

plasma optical

emission

spectrometry,bothofwhicharemassratiobased,rivalorevenexceedclassicalanalysisinprecision,accuracy,andspeed.

Nevertheless,gravimetry andtitrimetry willendureasaccurate,directlySItraceable,primarymethods,providedt att e r systemat cerrorsareproper yeva uate us ngthe

best

instrumental

techniques

available.


5/31

Gravimetri adalah enentuan kadar unsur atau un s esikimiadengancaramengukur berathasilreaksikimia

tidaklarut

yang

diketahui

dengan

pasti.

Hasilreaksiyangtidaklarutbisaberupagasyang

tidakmenguap,

baik

berasal

dari

penguapan

pada

suhurendahmaupundaripemijaranpadasuhutinggi.Padaumumnyayangdimaksudsenyawatidaklarutadalahendapanyangterbentukdidalamsuatu

Gravimetrimeru akanmetode an sudahdikenalse ak

abadke

16.


6/31

Titrimetriadalahmetodepenentuankadarunsuratauspesikimiadengancaramengukurjumlahsenyawa

kimia

yang

secara

pasti

diketahui

bereaksi

secara

ditentukantersebut.

Massakimia

tersebut

diukur

dari

sejumlah

volume

larutan

standar(baku)dengancaratitrasi.Ada4metode, ,

kompleksometri,antitrasioksidasireduksi.Titikakhir

titrasi

secara

klasik

ditentukan

dengan

mengamati

,selisihpotensialpadaelektroda,ataumengamatiperubahankonduktivitaslarutan.


7/31

T tr metr cmet o s

o

ana ys s

are

capa e

o

rap

an

convenientanalytedeterminationswithhigh accuracyand

.

betweentheanalyteand areagent,thetitrant:

whereAandTrepresenttheanalyteandtitrant,respectively,and

aandtarethestoichiometric coefficients.

Forvolumetrictitrations,theamount,nA,ofanalyteinthe

samp ecan eca cu a e us ng

nA

=

a/t

.

CTVTw ere T s econcen ra ono e ran ,an T s evo umeoftitrantneededtoreachtheendpoint.


8/31

Penentuan

a arsuatu

ana t

a am

arutan

memer u an

:

,

tersebutharuscepatdansempurna,dimanahargaadant

diketahui.2) Konsentrasilarutanpenitrasi,CT,harusdiketahuidengan

pasti.Larutanpenitrasiharusdibakukandengansenyawa

a u

pr mer

atau

t tras

engan

arutan

yang

ter uat

ar

senyawabakuprimer.

menggunakanindikatorwarnaataudenganinstrumen.Jika

menggunakaninstrumen

yang

dapat

mengukur

secara

berkelanjutan,makaakandiperolehkurvatitrasi. Caraini

biasadigunakanuntukmenentukankadarcampuranatau

un u men e e s a anya gangguan n er erens .


9/31

Syaratkhusus

analisis

titrimetri

:

Gunakanlarutanpenitrasiyangumumdanjenisanalit

yangbereaksi

dengan

penitrasi

tersebut,

metode

pembakuanlarutanpenitrasi,kestabilanlarutan

penitrasi,metodedeteksititikakhir,danhalhallainnya

yangpenting.

GHJeffery,JBassett,JMendham,RCDenney,VogelsTextbook

o uantitative Chemical Anal sis 5th edition.

HALaitinen,WEHarris,ChemicalAnalysis,2ndedition.


10/31

AcidBaseTitrations

Reaksitransfer

proton

di

dalam

larutan

air

berlangsungsangatcepat.

suitablefortheanalysisofanyBronstedacid

or ase.Pract ca y,t epKaorpK o t e

analyteshouldbe

less

than

about

10

(i.e.,

pKaorpKb


11/31

Inorderforthetitrationreactiontogotocompletion,a

strongacid

or

astrong

base

is

the

usual

choice for

a

titrantinacidbasetitrations.Thelevellingeffectin

aqueoussolutionsshouldbekeptinmind, however :

thestrongest

acid

that

can

exist

at

asubstantial

concentrationisthehydroniumion,H3O+, sinceany

strongacidHAwillreactcompletelywithwater:

HA + H O A + H O+

titratingtheanalytewithhydroniumion. Similarly,the

ion,OH.


12/31

Fortheanal sisofbases themostcommona ueoustitrant

is

HCl;

sometimes

H2SO4orHClO4are alsoused.Anyof

thesemaybestandardizedby

tris(hydroxymethyl)aminomethane,(HOCH2)3CNH2, whichis

sometimes

referred

to

simply

as

Tris.

, 2 3,

standard,butitislessdesirablethanTrisduetoitslower

e uivalent wei ht.

Titrationsof

bases

are sometimes

called

alkalimetric

titrations.

Fortheanalysisofacids,NaOHisusuallyused;KOH

orBa(OH)2may

also

be

used.

Any

of

these may

be

standardized

againstpotassiumhydrogenphthalate(KHP).Thehydrogen

phthalateanionis shownbelow.

trat onso ac saresomet mesca e ac metr ct trat ons.


13/31


14/31

Anyalkalinesolutionwillabsorbsubstantialamountsofcarbon

dioxidefrom

the

atmosphere, resulting

in

the

following

net

reaction : CO +2OH CO 2 +2H O

Exposureof

aqueous

NaOH

or

KOH

titrant

to

the

atmosphere

resu tsincar onateerror.

Solid hydroxidesaltsmayalsocontainsignificantamountsof

2.

NaOHtitrant

solution

is

best

prepared

by

dilution

from

a

concentrated (approximately50w/w%)solution.Sodium

carbonateisinsolubleinthissolution.Thedilutedtitrant

solutions

are

sometimes

boiled

to

drive

dissolved

CO2out

of

the

so ut onan t enprotecte rom exposuretoa r. ea sorpt on

processisfairlyslow,occurringoveraperiodofhoursanddays.

,

preparedand

standardized

solution of

NaOH.


15/31

additionofacidorbaseistermed thebufferingcapabilityofthe

solution.The

ability

of

anatural

water

body

to

resist

adecrease

in

Hisveryimportantduetotheubiquitouspresenceofacidrain.

Thealkalinityofawaterbodyisdefinedasthenumberofmolesof

nee e o r nga samp e op = . .

moreacidmustbeaddedtothe1 LsampletobringthepHto4.5.

Acidimetrictitration

to

pH = 4.5

(rather

than

to

an

endpoint)

is

thus

widelyusedtocharacterizethe abilityofawaterbodytoresist

acidification.Ifpotentiometricdetectionisnotused,bromcresol

indicator;the

color

change

signifies

the

end

of the

titration.


16/31

KJELDAHL apparatus


17/31

Kjeldahl Analysis of Organic Nitrogen

organic nitrogen in the 3 oxidation state. The sample is

di ested with sulfuric acid to convert the or anic nitro en

to ammonium, NH4+. The digested sample is then basified

and ammonia is then disti lled into acid. The ammonia maybe disti lled into excess standard HCl; the amount of HCl

remaining after the distillation is determined by alkali-

. ,

excess boric acid, H3BO3; the dihydrogen borate, H2BO3,

formed b reaction with ammonia is determined b

acidimetric titration. The total Kjeldahl nitrogen (TKN)

content of a water sample is a measure of the totalconcentration of nitrogen in the 3 oxidation state in the

sample: ammonia/ammonium plus organic nitrogen.

protein content of food samples.


18/31

Titrimetr Methods

PrecipitationTitrations

Precipitationreactions

in

aqueous

solution

range

from

rapi tos ow, epen ingont ei entityo t e

precipitant.

Manyprecipitationsaresufficientlyrapidandcomplete

to ormt e as so quant tat on yt trat on.

rec p tat ont tr metry assevera a vantagesover

precipitationgravimetry,including speed,sensitivity,and

conven ence.


19/31

ArgentometricTitrations+

, .

precipitationsarerapidand quantitative,andsilvernitrate,AgNO3,isusedforthedirecttitrationofanumberofanionsthat

precipitatesilver :allthehalidesexceptF;SCN,CNO,AsO43,

PO43

,CN

,C2O4

2

,CO3

2

,S

2

,CrO4

2

.ee a e onpage n arr s ormore e a .

Titrationsusin A NO astitrantare termedar entometric

titrations.Sodium

chloride

is

suitable

as

aprimary

standard,

and

is

mostoftenusedforstandardizationofthe titrantinargentometric

titrations.Solidsilvernitrateisalsoavailableinhighenoughpurity

toserve asaprimarystandard,butitismoreexpensive.

,

areusedforstorage.Exposuretolight cancausephotoreductionof

thesilvercations, articularinthe resenceoftraceim urities

that

may catalyze

the

reaction.


20/31

u a e

na ys sThesulfatecontentofanaqueoussolutionmaybe

,

BaCl2.Thetitrantisusuallystandardizedusingsodium

.

Fluoridecannotbeanalyzedbyargentometrictitration,

withlanthanumnitrate,La(NO3)3,orleadnitrate,

3 2, 3 . PbF2(pKsp=7.57)areinsoluble.Sodiumfluorideisa

.


21/31

EndpointDetection

Avarietyofchemicalindicatorsareusedtoindicatethe

, ,

somedetailinthelaboratory handoutTitrimetric

,

chapter7).

Asilverwireorringisasufficientindicatorelectrodefor

3, ISEissuitableforpotentiometricendpointdetectionfor

.


22/31

Example:AnalysisofChlorideinSurfaceWaters

Chlorideisfrequentlyamajoranioninsurfaceand

seawater.Althoughchlorideinfreshwaterisusuallyof

,

wintermaysignificantlyincreasethechloridecontentof

, .

concentrationmay

impart

anoticeably

salty

taste

to

,

growingplants.

methodforchloridedetermination; concentrationsin

potentiometrictitration.


23/31

TitrimetricMethods:

RedoxTitrations

Redoxreactionsarethemostdiverseofthefourmain

precipitation,complexationandredox).

analyze forany

oxidizing

or

reducing

agent.

However,

man redox reactions are eithertoo slowor have

inconsistentstoichiometry.Thestabilityoftitrantand

anal te solutions can also be a roblem.

Nevertheless a wide variet of anal tes can be

convenientlydetermined

by

redox

titrations.


24/31

Consideragenericredoxhalfreaction(chargesomitted

forclarity) : ox

+n

e

reAchemical(i.e.,oxinthisequation)thatpullselectrons

fromanothersubstanceisanoxidizing agent,whilea

chemical(red)

that

forces

another

substance

to

accept

electronsisareducingagent.

Together,ox/redformaredoxcouple;redoxcouplesare

analogousto

acid/base

conjugate

pairs.

And just

like

acidbasereactions,theconjugateofastrongoxidizing

agentisaweakreducingagent.

The

strength

of

oxidizing/reducing

agents

can

bededucedbythestandardreductionpotential:avery

positivestandardpotentialindicatesastrongoxidizing

agent,

while

a

low

positive

or

a

negative potential

is

characteristicofastrongreducingagent.


25/31

Thestrengthofanoxidizingorreducingagentisvery

.

acidicconditionstendtomakeoxidizingagentsmore.

fewredoxreagentsarerelativelyinsensitivetopH,which

.

MostredoxreagentsarestableonlywithinacertainpH

.

Sampletreatment

is

often

necessary

to

adjust

the

.

reducedorpreoxidized.Forprereductionoftheanalyte,

canbeused.Itiscommontouseareductor,whichisa

solutionis

poured.


26/31

Twocommon

reductors

are :

the

Jones

Reductor,

which

usesamal amatedzinc(ZnH ) ranules,andtheWalden

Reductor,whichusessilvergranules (chlorideisadded

tothe

sample,

usually

as

HCl).

The

Walden

Reductor

is

moreselective(i.e.,aless powerfulreducingagent)than

theJonesReductor.

Preoxidationisnotascommonasprereduction,since

theanalyteisusuallydesiredinareduced formfor

titrationwith

an

oxidizing

agent.

However,

when

pre

oxidationisnecessary,sodium bismuthate,NaBiO3,

ammoniumperoxydisulfate,(NH ) S O ,orhydrogen

peroxide

may

be

used.


27/31

TitrimetricMethods:

ComplexometricEDTA

Titrations

Complexometrictitrationsarebasedonthereaction

betweenLewis

acids

(usuall

metal

cations)

and

Lewisbases. M+:L M:L .

donatestwo

electrons

to

form

abond

withthe

acid.

Since

+ , , ,

BronstedbasewillbeaLewis base.Lewisbaseswill

donatetotheLewis acid.Lewisbasesarealsosometimes

,

theligandbinding

site.


28/31


29/31

Aspecialsubsetofligandsarethosethatcontainmore

an

one

n ng

s e

on

e

mo ecu e;

ese are

ca e

chelatingagents.Chelatingagentsformparticularly

.

Byfarthemostcommoncomplexometrictitrantis

, .hexadentatechelatingligand,meaningthattherearesix

.

EDTAtitrations

are

very

versatile:

they

can

be

used

for

metals,andcanevenbeused(throughbacktitration

.

EDTAtitrationsarealsofairlysensitive,capableof

approximately10

ppm

(i.e.,

10

mg/L).


30/31

AdvantagesofEDTAasaComplexingTitrant

Complexationofmetalcationswithunidentateligandsisnot

wehaveasolutionofCu2+ tobeanalyzedbycomplexometric

titration.Wecanuseatitrantsuchasaqueousammonia,aunidentate

ligand.Thefollowingequationsshowthe stepwiseformationof

comp exes e ween eme a an e gan :

2++ 2+ =

CuNH32+ +NH3 Cu(NH3)2

2+ logK=3.34

Cu(NH3)22+

+

NH3 Cu(NH3)32+

logK

=

2.73Cu(NH3)3

2++NH3 Cu(NH3)42+ logK=1.97

nce ecoor na onnum ero u , ea ywewou o serve

fourdistinct

endpoints

during

the titration

with

NH3.


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Documents

01. Analisis Farmasi Anorganik