Titration l2h

TITRATION QUALITY CONTROL with Drug Assay

TITRATION   

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“titalus” (Latin) – inscription or title “titre” (French) – rank a common laboratory method of quantitative/chemical analysis that can be used to determine the concentration of a known reactant (analyte) The basis of the method is a chemical reaction of a standard solution (titrant) with a solution of an analyte. Because volume measurements play a key role in titration, it is also known as volumetric analysis 

Usually, it is the volume of the titrant required to react with a given quantity of an analyte that is precisely determined during a titration.

TITRATION 

The process of adding a measured amount of a standard solution to a specified amount of sample solution in order to find the concentration of a certain ion in the sample solution.

BASICS OF TITRATION

Essentials of Titration 

Titrant

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Analyte

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Indicator

Setup for a Typical

Essentials of Titration 

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Titrant (or Standard Solution) - A solution of known concentration used in a titration Analyte (or Titrand or Sample solution) – is a solution of the substance whose concentration is unknown and sought in the analysis Indicator - A substance which will change colour or do something else to show that the titration is complete

Titrant / Standard Solutions 

Standard Acid Solutions  

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Hydrochloric Acid Sulfuric Acid

Standard Alkali Solutions   

Sodium hydroxide Potassium hydroxide Barium hydroxide

Standard Acid Solutions 

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HCl is preferred in the titration of compounds that yield precipitate, such as Ba(OH)2 H2SO4 is preferred in hot titrations, since HCl losses chlorides during volatilization

Standard Alkali Solutions 

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Alkali solutions absorb carbon dioxide from the air  changing rapidly in concentration NaOH and KOH may become contaminated with carbonates  liberation of CO2 during acid – alkali titration Ba(OH)2 solutions is free from carbonates  CO2 is pptd. as BaCO3 thus decreasing the conc. of Ba(OH)2 in sol’n Alkali sol’ns should be restandardized frequently

Indicators

Three (3) Theories in the change of color of indicators: 

Physicochemical Theory – change in color is due to increase or decrease in certain ions 

Methyl Red, Phenolphthalein, Methyl Orange  

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Organic Theory – the color of the indicator is due to certain groupings of the elements in a compound and the change in color is due to change in molecular structure 

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Increase in ions – appearance of new color Decrease in ions – disappearance of a color or the appearance of a different color

Eriochrome Black, Hydroxynaphthol blue, Xylenol orange, Pyridylazonaphthol

Colloidal Theory – assumes that indicators form a colloidal solutions and change in color is dependent on the change in size of the colloidal particle 

Eosin Y, TEE, DCF

Rules in the Use of Indicator 1. 2.

3. 4. 5.

6.

Use 3 drops of indicator unless otherwise directed. Strong acid titrated with Strong Alkali (vice versa) Methyl Red, Methyl Orange, Phenolphthalein Weak Acid titrated with Strong Alkali  Phenolphthalein Weak Alkali titrated with Strong Acid  Methyl Red Weak Alkali should never be titrated with Strong Acid, or vice versa, since no indicator will give a sharp end point. The appearance of a color is more easily observable than is the disappearance  always titrate where possible to the appearance of a color

Mixed Indicators use to sharpen up the color change Methylene Red – Methylene Blue Xylene Cyanol – Methyl Orange Bromocresol Green – Methyl Red Bromocresol Green – Chlorophenol Red Cresol Red – Thymol Blue Thymol Blue – Phenolphthalein

Equipments used: 

Volumetric Apparatus 

To deliver a definite volume of liquids  Burettes

/ Burets  Pipets / Pipettes 

To contain a definite volume of liquids  Volumetric

flasks  Graduated cylinders

Sources of Error in the Use of Volumetric Apparatus  

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Water adhering to apparatus Rinse and discard washings Grease films and dirty apparatus cause irregularity in the delivery of liquids and distort the meniscus rinse the apparatus prior to usage Parallax must be a voided  proper readings must be practice always Variations in temperature leads to change in volume of the vessels and liquids  measurements must be done at a temperature closely approximating to that of the calibration of the vessel Air bubbles trapped beneath the liquid surface, specially below buret’s stopcock  displace liquid Heat coming from hot solutions causes change in volume  let it cool Most salts dissolved produce a change in temperature, with concomitant change in volume of the solution  acquire the temperature at which the apparatus is calibrated Failure to used the apparatus properly  learn more about what you are using

Equipments used: 

Volumetric Apparatus     

Buret Pipette Buret funnel Volumetric Flask Erlenmeyer Flask (usually 250 mL)  Beaker,

250ml  Stirring rod 

pH meter

Buret  

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Also “burette” is a device used in analytical chemistry for the dispensing of variable, measured amounts of a chemical solution

Buret 

Classification: 

Class A

Class B

10

0.02

0.04

25

0.03

0.06

50

0.05

0.10

100

0.10

0.20

Analogue     

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A traditional burette consists of glass tube of constant bore with a graduation scale etched on it and a stopcock at the bottom The barrel of the stopcock may be made of glass or the plastic PTFE. Stopcocks with glass barrels need to be lubricated with vaseline or a specialized grease. Burettes are manufactured to specified tolerances, designated as class A or B and this also is etched on the glass Temperature and grade are shown at the top.

Digital    

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Burette accuracy /mL

Volumetric burette delivers measured volumes of liquid 

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Capacity, mL

based on a syringe design The barrel and plunger may be made of glass. With liquids that corrode glass, including solutions of alkali the barrel and plunger may be made of polyethylene or another resistant plastic material. The barrel is held in a fixed position and the plunger is moved incrementally either by turning a ratcheted wheel by hand, or by means of a step-motor. The volume is shown on a digital display.

Piston burettes are similar to syringes, but with precision bore and plunger, manually operated or motorized Weight burette delivers measured weights of liquid

Buret   

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is a cylindrical tube with a stopcock at one end made “to deliver” definite volume of liquid carefully calibrated piece of instrument that is used to measure out an exact amount of solution. Graduated in 0.1 mL increments Types: 

Acid Burette (Geissler)  

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Geissler Buret w/ glass stopcock – with a ground glass stopcock Geissler Buret w/ Teflon stopcock – stopcock and tip are polymethylpentene (PMP) with leakproof, self lubricating Teflon stopcock plug. For dilute acids and bases but avoid alcohol and organic bases. Economy grade.

Base Burette (Mohr) with a pinchcock as its stoppers

Geissler Buret Geissler Buret with Teflon stopcock

Geissler Buret with Glass stopcock

Mohr Buret

Using a Buret 

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Always rinse buret with water (from a beaker, not the faucet) first. Second, rinse(2-3 times) with a small amount of the titrant and drain it through the tip. Check if the buret is flowing freely. To fill a buret, close the stopcock at the bottom and use a funnel. You may need to lift up on the funnel slightly, to allow the solution to flow in freely. Do not waste time trying to fill the buret to zero for each titration.

Using a Buret 

You can also fill a buret using a disposable transfer pipet. This works better than a funnel for the small, 10 mL burets. Be sure the transfer pipet is dry or conditioned with the titrant, so the concentration of solution will not be changed.

Using a Buret 

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Fill the buret tip by momentarily opening the stopcock. Check the tip of the buret for an air bubble. To remove an air bubble, whack the side of the buret tip while solution is flowing. If an air bubble is present during a titration, volume readings may be in error.

Using a Buret 

Rinse the tip of the buret with water from a wash bottle and dry it carefully. After a minute, check for solution on the tip to see if your buret is leaking. The tip should be clean and dry before you take an initial volume reading.

Using a Buret 

When your buret is conditioned and filled, with no air bubbles or leaks, take an initial volume reading. A buret reading card with a black rectangle can help you to take a more accurate reading. Read the bottom of the meniscus. Be sure your eye is at the level of meniscus, not above or below. Reading from an angle, rather than straight on, results in a parallax error. that burets are graduated in a downward direction. The first estimated digit will probably be the hundredths place.

Using a Buret 

Deliver solution to the titration flask by turning the stopcock. The solution should be delivered quickly until a couple of mL from the endpoint.

Using a Buret 

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The endpoint should be approached slowly, a drop at a time. Use a wash bottle to rinse the tip of the buret and the sides of the flask. Do not start above the 0 mL mark or titrate past the 50 mL mark.

Titration Notes 

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Always use white paper underneath your sample flask so that you will notice slight color changes. Learn to swirl the flask without removing it from underneath the buret. Use a drop, drop, drop pace until you see the color change becoming more than local (where the titrant meets the sample). Now proceed dropwise. Second and third trial titrations should always be fast assuming the sample will be about the same because you now know approximately how much titrant is needed. If the first titration required 25 mL than you can add 22 mL all at once and then proceed cautiously. that the amount of water used to dilute the sample is not crucial because it does not affect "how many" of the sample molecules are present in the sample flask. Diluting with water allows you to see the color change easier. Always label multiple burets and sample flasks. to add indicator.

Pipettes / Pipets Used to deliver or measure standard volume of liquid  Common pipets: 

 Air

displacement micropipettes  Positive displacement pipette  Volumetric pipettes  Graduated pipettes  Pasteur pipette  Transfer pipettes

Volumetric pipettes 

or “bulb pipette” – allow the to measure a volume of solution extremely accurately (accuracy of four significant figures).

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Aka: TRANSFER or DELIVERY PIPETS

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These pipettes have a large bulb with a long narrow portion above with a single graduation mark as it is calibrated for a single volume (like a volumetric flask).

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Usually available in 1ml, 2ml, 5ml, 10ml, 25ml, 50ml, 100ml

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Volumetric pipettes are commonly used to make laboratory solutions from a base stock as well as prepare solutions for titration

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Used for accurate measurements since it is designed to deliver only one volume

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Accurate and precise measurement accurate to four significant figures

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Designed such a fluid is dispensed, a small drop of liquid will remain in the tip  DO NOT BLOW  let the tip touch the wall of the flask and give a half - twist

Specifications on Volumetric Pipettes The following must be indicated How much liquid will be transferred if the liquid is drawn up to the calibration line on the neck The temperature at which the calibration was made

Graduated pipettes  

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Aka: MEASURING PIPET are a type of macropipette consisting of a long tube with a series of graduations, as on a graduated cylinder or burette, to indicate different calibrated volumes Graduated pipettes are often graduated in one of two ways: 

Mohr, backward or drain-out pipettes 

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The graduation on these always end before the tip

Serological, forward or blow-out pipettes 

The graduation marks continue to the tip

Graduated pipettes A Mohr, backward or drain-out pipette

Serological, forward or blow-out pipette

Specifications on Measuring Pipet Printed on the neck of the pipette are the specifications that indicate: The maximum volume of liquid that can be transferred The size of the divisions on the pipet The temperature at which calibrations were made If the pipette is a “to deliver” (TD) or “to contain” (TC) pipette

Pasteur pipettes 

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are plastic or glass pipettes used to transfer small amounts of liquids, but are not graduated or calibrated for any particular volume they are also called as teat pipettes, droppers, eye droppers and chemical droppers

Standard method of TITRATION  

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A known volume of the analyte is placed in a titration flask. The burette is filled by a standard solution (titrant,) of known concentration. Before the titration is started, 1-3 drops of indicator (phenolphthalein) is placed in the titration flask with the analyte. The chosen indicator must be one color when the solution is acidic. A base solution is then slowly added from the burette, drop by drop. The titration continues, drop by drop, until the indicator suddenly achieves the intermediate color (weak pink) between that of the acid and the color of the base (fuchsia). At that point the titration ceases. The point at which the system is neither acidic or basic is referred to as the endpoint. The endpoint will correspond to a perfect stoichiometric relationship between the acid and the base. Once the endpoint has been reached, the burette must be read. The bottom of the meniscus line determines the quantity of the base that was required to reach the endpoint. Once the titration is completed, the final calculations can be done.

Titrating with a pH meter 

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Titration with a pH meter follows the same procedure as a titration with an indicator, except that the endpoint is detected by a rapid change in pH, rather than the color change of an indicator. Arrange the sample, stirrer, buret, and pH meter electrode so that you can read the pH and operate the buret with ease.

Definitions: 

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Standard Solution – a solution of known concentration Standardization  

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Primary Standard Secondary Standard

Titer

Titrimetry 

measuring the quantity of a reagent of known concentration required to react with a measured quantity of sample of an unknown concentration

Titrimetry Types   

Volumetric Titrimetry Gravimetric or Weight Titrimetry Coulometric Titrimetry

Titrimetry Types 

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Volumetric Titrimetry - involves measuring the volume of a solution of known concentration that is needed to react completely with the analyte. Gravimetric or Weight Titrimetry - differ only in that the mass of the reagent is measured instead of its volume. Coulometric Titrimetry - The reagent is a constant direct electrical current of known magnitude that consumes the analyte, the time required and thus the total charge to complete the electrochemical reaction is measured.

Titration Reaction types

Acid-Base Titrations Titration Reaction types

Acid-Base Titrations 

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a process of neutralization whereby a titrant (a solution of known concentration) is delivered into an analyte (unknown solution) until the unknown solution is completely neutralized An indicator is (often) a weak acid that is placed into the unknown solution to determine the endpoint of the titration (the pH at which the indicator changes color) The equivalence point of the titration is the point when the moles of H+ are equal to the moles of OH- in a titration The progress of an acid-base titration is often monitored by plotting the pH of the solution being analyzed as a function of the amount of titrant added. The graph produced is called a Titration Curve.

Types of acid-base Titrations 

Strong Acid / Strong Base 

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Weak Acid / Strong Base 

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pH at equivalence point = 7 pH at equivalence point >7

Strong Acid / Weak Base 

pH at equivalence point <7

Note: weak acid / weak base titrations are too complicated and are almost never carried out.

Indicators of Acid – Base Reactions

Applications of acid-base titration 

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In the determination of iron in pharmaceutical preparations First of all, acid-base titration, to control acidity or alkalinity of solutions, to do neutralization tests and analyze mixtures of acids Wide use is in titration processes

RedOx Titrations Titration Reaction types

RedOx Titration 

Titration of a reducing agent by an oxidizing agent or titration of an oxidizing agent by a reducing agent. The concentrations of redox-active species can be determined by redox titrations. In a redox titration, a measured sample of the unknown is titrated against a standard solution of a substance that will oxidize or reduce the unknown.