Titrations

Sujinda Rojanasaksothorn

Bureau of Drug and Narcotic

Department of Medical Sciences

9 March 2012

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Titrations

• Definition

• ปฏกรยา ในการ titrate (ประเภท Rx)

acid-base, redox, complexometric, precipitate titrations

• ชนดของการ titrate : Direct , Back titrations

• วธการ titrate : visually, instrumentally titrations

• Aqueous / Non-aqueous Titration

• การคานวน

• อนๆ

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Definition• The molegular weight ( gmw, MW) /the gram formular weight (gfw)/ is

summation of atomic weights, in gram, of all the atoms in the chemical formula

of a substance.

• For H2 is 2.016 (2x 1.008)g; For NaCl it is 58.44 (22.99+35.45) g .

• BP : Molarity ,M M = no. mole / 1 L = น.น. สาร / MW

liter of solution

• Mole no. mole = มวล (g)/ มวลโมเลกล (g)

• USP : Normality,N N = no. eq / 1L = น.น. สาร / eq wt

liter of solution

• Equivalent (eq) no. eq = มวล (g) / eq wt (g)

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Definition• The equivalent weight (eq wt) :

• eq wt in a neutralization reaction : weight which either contributes or reacts with one gram hydrogen ion.

- NaOH, HCl each has only a single reactive hydrogen ion or hydroxide ion

eq wt = MW

- H2SO4 : strong acid ให 2 H + ; H2SO4 : 0.5 M = 1 N

eq wt = one – half its MW 1 M = 2 N

= MW / 2 MW / L = 2 (MW/2 / L)

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USP : Volumetric Solution ; H2SO4 1 N

MW : 98.08 g

49.04 g in 1 L or 30 ml dilute to 1020 ml

BP : Volmetric Solution ; H2SO4 0.5 M

MW : 98.08 g 28 ml dilute to 1 L

Definition

• eq wt in a Redox reaction :

• weight which consumes or produces one mole electrons.Mn+7O4

- + 5 e + 8 H+ Mn2+ +4 H2O ;

• KMnO4 MW= 158 g ; eq wt = MW/5 = 158/5 = = 31.6 g

• BP : Volumetric solutions For a 0.02M solution KNnO4

- Dissolve 3.2 g (158x0.02) of KMnO4 in 1000 ml of water

• USP : Volumetric solutions For KMnO4 , 0.1 N

• KMnO4, 158.03

• Dissolve about 3.3 g of KMnO4 in 1000 mL of water

• KMnO4 solution 0.02 M = 0.1 N5

Titrations USP 34 : General Charpters \ General Test and Assay \ Other Test and Assay \ <541> Titrimetry

BP 2008 : Search “ Titrimetric”

Supplementary Chapter VI B : Titrimetric Analysis

Appendix VIII A. Non-aqueous Titration

Appendix VIII B . Potentiometric Titrations

Volumetric Solutions USP 34: Reagents \ Solutions \ Volumetric Solutions

BP 2008 : Appendix 1 B. Volumetric Reagents and Solutions

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USP <541> Titrimetry

• Direct Titrations

• Residual Titration / Back Titrations

• Complexometric Titrations

• Oxidation-Reduction Titrations

• Titration in Nonaqueous Solvents

• Indicator and PotentiometricEndpoint Detection

• Blank Corrections

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BP : Supplementary Chapter VI B

B. Titrimetric Analysis

•Acid-base titrations

•Redox titrations ประเภทRx

•Complexometric titrations

•Precipitation titrations

•Direct titrations วธการ titrate

•Back titrations

•Measuring the equivalence point

•Indicators

Appendix VIII A. Non-aqueous titration

Appendix VIII B . Potentiometric

Titrations

Titration Reactions

• Acid-base titrations

The neutralisation reactions that occurs between an acid and a base.

HCl + NaOH NaCl + H2O

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• Redox Titrations

The transfer of electron between a reducing agent and an oxidizing agent

Oxidizing agents :

iodine, potassium permanganate solutions

Reducing agent s :

sodium thiosulfate, oxalic acid, ammonium iron(II) sulfate solutions

2 S2O3 3- + I 2 S4O6

2- + 2 I - indator : Starch solution

• Complexometric Titrations

The formation of a complex between a chelating agent and a metal cation.

Complexing reagent : EDTA : Ethylene diaminetetraacetic acid (H4Y)

disodium edetate : C10H 14N2Na2O8 . 2H2O, H2Na2Y; MW 372.24

Cation : calcium, magnesium, copper, zinc, aluminium ion

Ca 2+ + Y 4+ CaY 2+ ( ind. : Eriochorme BT)

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• Precipitation titrations

The determination is base on the formation of an insoluble salts under certain

condition.

The titration of halides ( in particular chloride ions) with silver ion

NaCl + AgNO3 AgCl + NaNO3

Titration Reactions

Direct Titrations (Forword Titration ):

• In a direct or forward titration the analyte reacts directly with the titrant.

• The treatment of a soluble substance, contained in solution in a suitable vessel

(the titrate), with an appropriate standardized solution (the titrant), the endpoint

being determined instrumentally or visually with the aid of a suitable indicator.

• The quantity of the substance being titrated may be calculated from

- the volume of the titrant (volumetric solution)

- the normality or molarity factor of the titrant (M / N)

- the equivalence factor (titer) for the substance given in the individual

monograph

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Direct Titrations

Direct TitrationAssay for Fusidic Acid (BP)

• Dissolve 0.500 g in 10 ml of alcohol R.

• Add 0.5 ml of phenolphthalein solution R.

• Titrate with 0.1 M sodium hydroxide until a pink colour is obtained.

• 1 ml of 0.1 M sodium hydroxide is equivalent to 51.67 mg of C31H48O6

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Titrant = 0.1 N NaOH indicator : phenolphthalein solution R

Fusidic acid 51.67 mg ใช 0.1 N NaOH 1 ml

500 mg “----------------” 1x500/51.67 = 9.6 ml

ควรใช burette ขนาด 25 ml End point ~ 10 ml

Standardized ทราบ Molarity / Normality ดาง

1 ml of 0.1 M sodium hydroxide is equivalent to 51.67 mg of C31H48O6

end point = V ml , หาน.น. สารในผงยา : = V (ml) x N /0.1 x titer = X mg

ใน น.น. ผงยา ทชง W (mg) ม สารทสนใจ X mg

ใน น.น ยาตอ 1tab wt/unit (mg) ม สารทสนใจ X (mg) x wt/unit (mg)

W (mg)

ปรมาณตวยา / tab = V(ml) x N (mol/L) x Titer (mg) x wt/unit (mg)

1 (ml) x 0.1 (mol/L) x W (mg)

mg/tab = V /1 x M /0.1 x titer x wt/unit / น.น.ผงยา ทชง

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Ditrect Titrations

Residual / Back Titrations

USP The addition of a measured volume of a volumetric solution,in excess of the amount actually needed to react with the substance being assayed,the excess of this solution then being titrated with a second volumetric solution. This constitutes a residual titration and is known also as a “back titration.”

BP• Add an excess of the reagent and then determine the excess by back-

titration with a second reagent of known concentration

• เปนการเตม VS (#1) ในปรมาณทเกนพอกบการทา ปฏกรยาของสาร แลว titrate หา

ปรมาณทเกนพอ ดวย VS (#2) ทร concentration

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The quantity of the substance being titrated may be calculated from

the difference between the volume of the volumetric solution originally

added, corrected by means of a blank titration, and that consumed by

the titrant in the back titration, due allowance being made for the

respective normality or molarity factors of the two solutions, and the

equivalence factor for the substance given in the individual monograph.

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Residual / Back Titrations

BP: Back titrations

- The term back titration is used when a titration is done "backwards” instead of titrating the original analyte, a volumetric solution of a reagent is added to the solution to react with the analyte, then the excess reagent is titrated.

- The end point of the reverse titration is easier to identify than the end point of the normal titration.

- The reaction between the analyte and the titrant is very slow.

- They may also be used where direct titrations are unsuitable for technical reasons

the sample is not soluble in water

the sample contains impurities that interfere with forward titration.

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Residual / Back Titrations

Examples of back titrations : Assay for Aspirin Tablets (BP)

• Weigh and powder 20 tablets. To a quantity of the powder containing

0.5 g of Aspirin add 30 ml of 0.5M sodium hydroxide VS, boil gently

for 10 minutes and titrate the excess of alkali with 0.5M hydrochloric

acid VS using phenol red solution as indicator. Repeat the operation

without the substance being examined. The difference between the

titrations represents the amount of sodium hydroxide required.

• Each ml of 0.5M sodium hydroxide VS is equivalent to 45.04 mg of

C9H8O4.

Residual / Back Titrations

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Assay : Back Titration Blank titration/ Volume relationship

0.5 g Aspirin 30 ml 0.5M NaOH VS

+ 30 ml 0.5M NaOH (VS #1)

titrate the excess of 0.5M NaOH with 0.5M HCl (VS #2)

with 0.5M HCl (VS #2) titrant

End point : V1 End point : V2

คานวน :

Each ml of 0.5M sodium hydroxide VS is equivalent to 45.04 mg of C9H8O4

mg/tab = (V2-V1) x Nกรด /0.1 x 45.04 x wt/unit / น.น.ผงยา ทชง

mg/tab = 30-(V1 x 30 / V2) x Nดาง /0.1 x 45.04 x wt/unit / น.น.ผงยา ทชง

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Residual / Back Titrations

กรดV2 ดาง 30

V1 V1 x 30 / V2

Indicators

• Indicators are used to provide a visual determination of the end point of a

reaction. This may be by a change in colour or the formation of a precipitate.

Acid/base indicators : Phenolphthalein , Bromocresol green, Methyl orange.

Redox indicators : Nitrophenanthroline, Methylene blue , Ferroin

Complexometric indicator : Eriochrome Black T, Xylenol orange

Precipitation indicator : Fluorescein , Eosin

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Visually Titrations : Indicators

Instrumentally titratipns : Potentiometric titrations

• End point determination results from the use of electrochemical measurements.

• เปนการวดความเปลยนแปลงของ ศกดไฟฟา (mV) ของสารละลาย กอนและหลง

การ titrate โดยการใช indicator electrode และ referent electrode จมในสารละลาย

• เมอทาการ plot mV กบ ml totrant added จะได sigmoid curve (S-shape)

• The midpoint of this linear vertical portion or the inflection point may be taken as

the endpoint.

• The equivalence point may also be determined mathematically without plotting a

curve.

• Table 2. “Potentiometric Titration Electrode Systems” <541>

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Combined silver ring electrode for argentometric titration: DM141

Combined platinum ring electrode for redox titration : DM 140 SC

Combined pH glass electrode for titration in aqueous solutions : DG 111 SC

Combined pH glass electrode for titration in non-aqueous solutions : DG 113 SC

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Non-aqueous TitrationsUSP

• Many water-insoluble compounds acquire enhanced acidic or basic

properties when dissolved in organic solvents.

• Thus the choice of the appropriate solvent permits the determination of a

variety of such materials by nonaqueous titration.

• Many salts of halogen acids may be titrated in acetic acid or acetic

anhydride after the addition of mercuric acetate, which removes halide ion

as the unionized mercuric halide complex and introduces the acetate ion.

• Titrant of a basic compound : 0.1 N perchloric acid in glacial acetic acid

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Non-aqueousTitrations

• Titrant of an acidic compound :

0.1 N sodium methoxide in a mixture of methanol and toluene

0.1 N tetra-n- butylammonium hydroxide a mixture of methanol and toluene

• Interference by CO2, solvents for acidic compounds need to be protected from

excessive exposure to the atmosphere by a suitable cover or by an inert

atmosphere during the titration.

• Absorption of carbon dioxide may be determined by performing a blank titration.

• The blank should not exceed 0.01 mL of 0.1 N sodium methoxide VS per mL of

solvent.

• The endpoint may be determined visually by color change or potentiometrically

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Titration in Non-aqueous Sovent

BP 2008 : Appendix VIII A. Non-aqueous titration

Method I :

• Solvent : anhydrous acetic acid (previously neutralised using the indicator specified in the monograph)

• Titrant : 0.1 M perchloric acid VS

• When the substance is a salt of hydrochloric or hydrobromic acid, add 15 ml of mercury(II) acetate solution before neutralising the solvent, unless otherwise directed in the monograph.

Method II :

• The titrant, solvent and, where necessary, the indicator to be used are stated in the monograph.

• Protect the solution and titrant from atmospheric carbon dioxide and moisture throughout the determination.

• The solvent previously neutralised to the indicator

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อน ๆ

USP

• Blank Determinations—Where it is directed that “any necessary correction” be

made by a blank determination.

• Preparation and Methods of Standardization of Volumetric Solutions

The following directions give only one method for standardization, but other

methods of standardization, capable of yielding at least the same degree of

accuracy, may be used.

The values obtained in the standardization of volumetric solutions are valid for all

Pharmacopeial uses of these solutions, regardless of the instrumental or chemical

indicators employed in the individual monographs.

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Volumetric Solutions USP <541>

• Normal Solutions—Normal solutions are solutions that contain 1 gram

equivalent weight of the active substance in each 1000 mL of solution; that is, an

amount equivalent to 1.0079 g of hydrogen

• Molar Solutions—Molar solutions are solutions that contain, in 1000 mL,

1 gram-molecule of the reagent.

• Thus, each liter of a molar solution of sulfuric acid contains 98.07 g of H2SO4

• each liter of a molar solution of potassium ferricyanide contains 329.25 g of

K3Fe(CN)6.

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Volumetric Solutions USP <541>

• USP 29 : Hydrochloric Acid, Normal (1 N)

• HCl, 36.46

• 36.46 g in 1000 mL

• Dilute 85 mL of hydrochloric acid with water to 1000 mL. Standardize the solution as

follows.

• Accurately weigh about 5.0 g of tromethamine, Previously dried at 105 0C for 3 hours.

Dissolve in 50 mL of water, and add 2 drops of bromocresol green TS. Titrate with 1

N hydrochloric acid to a pale yellow endpoint. Each 121.14 mg of tromethamine is

equivalent to 1 mL of 1 N hydrochloric acid.

• N = mg tromethamine

121.14 x ml HCl

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Volumetric Solutions USP <541>

• USP 34 : Hydrochloric Acid, Normal (1 N)

• HCl, 36.46

• 36.46 g in 1000 mL

• Dilute 85 mL of hydrochloric acid with water to 1000 mL. Standardize the solution as follows.

• Accurately weigh about 5.0 g of tromethamine, dried according to the label instructions. Dissolve in 50 mL of water, and add 2 drops of bromocresolgreen TS. Titrate with 1 N hydrochloric acid to a pale yellow endpoint. Each 121.14 mg of tromethamine is equivalent to 1 mL of 1 N hydrochloric acid.

• N = mg tromethamine

121.14 x ml HCl

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อนๆ

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• 1. การจบบวเรตตเพอปลอยสารละลายออกจากบวเรตต ควรจดใหถกวธคอจบบวเรตตดวยมอซาย จบฟลาสดวยมอขวาขณะไทเทรตปลายบวเรตตจะตองจมอยในปากฟลาส 2. ขณะไทเทรตควรใชกระดาษสขาววางไวใตฟลาส เพอใหสงเกตการเปลยนแปลง สไดอยางชดเจน 3. ในระหวางการไทเทรตควรมการลางผนงดานในของฟลาสเพอใหเนอสารทตดอยขาง ๆ ไหลลงไปทาปฏกรยากนอยางสมบรณ 4. เมอการไทเทรตใกลถงจดยตควรหยดสารละลายลงในบวเรตตทละหยดหรอทละหนง หยด เพอปองกนการเตมสารละลายลงไปมากเกนพอ การหยดสารละลายทละครงหยดทาไดโดยเปดกอกเพยงเลกนอย เมอสารละลายเรมไหลมาอยทปลายบวเรตตกปดกอกทนท แลวเลอนฟลาสมาแตะทปลายบวเรตตใชน าฉดลางลงไปในฟลาส 5. เมออนดเคเตอรเปลยนส ควรตงสารละลายทงไวประมาณ 30 วนาท หากสไมเปลยนแปลงแสดงวาถงจดยตแลว 6. อานปรมาตรของสารละลายทใชในการไทเทรตโดยดตรงสวนโคงเวาตาสดวาตรงกบขดบอกปรมาตรใด

ขอแนะนา ตามปกตการไทเทรตจะตองทาซา 2-3 ครง ดงนนเพอความสะดวกและรวดเรวในการทดลอง การไทเทรตครงแรกอาจไขสารละลายจากบวเรตตลงไปอยางรวดเรว เพอหาจดยตอยางคราว ๆ หรอหาปรมาตรของสารละลายโดยประมาณกอน ในการไทเทรตครงท 2 หรอ 3 ตอนแรกอาจไขสารละลายจากบวเรตตเรวไดแตพอใกลจะถงจดยตกหยดสารละลายลงไปทละหยดเพอใหปรมาตรทใชในการไทเทรตมความเทยงตรงและไมมากเกนพอ

Record the volume reading from the buret. Determine the volume by reading from the bottom of the meniscus at eye level. All certain digits and one uncertain digit should be recorded.

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อนๆ

30

Burette to measure accurately the volume of a solution added. The scale can be

read to an accuracy of half a division, that is to 0.05 cm3.

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24.22 24.25

25

1 ml ม 10 ขด ความละเอยด = 0.1 ml

การอานไดถกตอง = 0.1/2 = 0.05

อนๆ

• Parallax is a deceptive change of the position of an object which is observed

while the position of the observer changes. Position of eye at all volumetric

vessels must be at the same level as the meniscus. If not, the parallax will cause

an error while reading the position of the meniscus of a liquid in a burette. It will

be a positive mistake if the eye is lower, and negative if the eye is higher than the

meniscus plane. parallax

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• Reference :• The United States Pharmacopeia. The United States Pharmacopeia Convention.

Rockville, MD.

• British Pharmacopoeia. The Stationery Office, London.

• Douglas A.Skoog and Donald M. West, “ Fundamentals of Analytical

Chemistry”, 3th ed. The United States of America. 1976.

• Mettler Toledo DL55 Titrator Operating Instruction, Mettler Toledo AG,

Analytical, Schwerzerbach, 1995.

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Work Sheets of Titrations

• “Titration : Standardization” : WS 2202080/1, Rev. no. 1

• “Direct Titration : Assay ” : WS 2202080/2, Rev. no. 1

• “ Titrimetric Method : Back Titration” : WS 2202080/3, Rev. no. 0

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สวสด

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Volumetric Solutions

• Iodine VS I2 = 253.8

• For a 0.5 M solution Dissolve 127 g of iodine and 200 g of potassium iodide

in sufficient water to produce 1000 ml.

• Ascertain its exact concentration in the following manner. To 2 ml of the solution

add 1 ml of 2M acetic acid and 50 ml of water . Titrate with 0.1M sodium

thiosulphate VS using starch solution as indicator. Each ml of 0.1M sodium

thiosulphate VS is equivalent to 12.69 mg of I.

• Store protected from light.

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Volumetric Solutions• Iodine, Tenth-Normal (0.1 N) (USP)

• I, 126.90

• 12.69 g in 1000 mL

• Dissolve about 14 g of iodine in a solution of 36 g of potassium iodide in 100 mL of

water, add 3 drops of hydrochloric acid, dilute with water to 1000 mL, and standardize

the solution as follows.

• Transfer 25.0 mL of the iodine solution to a 250-mL flask, dilute with water to 100 mL,

add 1 mL of 1 N hydrochloric acid, swirl gently to mix, and titrate with 0.1 N sodium

thiosulfate VS until the solution has a pale yellow color. Add 2 mL of starch TS and

continue titrating until the solution is colorless.

• Preserve in amber-colored, glass-stoppered bottles.

• N = ml Na2S2O3 x N Na2S2O3

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