Titration method of analysis


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Titration method of analysis

  1. 1. TITRIMETRIC ANALYSIS Siham Abdoun Msc., PhD
  2. 2. Introduction  A chemical test is a qualitative or quantitative procedure designed to prove the existence of, or to quantify, a chemical compound or chemical group with the aid of a specific reagent.  A presumptive test is specifically used in medical and forensic science.
  3. 3.  Pharmaceutical analysis is the quantitative measurement of the active ingredient and related compounds in the pharmaceutical product 1].  These determinations require the highest accuracy, precision, and reliability because of the intended use of the data as in: 1. Manufacturing control (identify drug in formulation),
  4. 4. 2. Stability evaluation (determine the impurity and degradation products in the stability study), and shelf-life prediction. 3. Determination of drugs and their metabolites in biological samples, generally plasma or urine, is important in elucidation of drug metabolism pathways as well as comparing bioavailability of different formulas.
  5. 5.  There are several methods used in chemical analysis starting from simple manual method to complicated and sophisticated ones of these are: titration, spectrophotometric ,HPLC with multi detectors ,……….etc
  6. 6.  Titration  Titration involves the addition of a reactant to a solution being analyzed until some equivalence point is reached. Most familiar one is the acid-base titration involving a color changing indicator. There are many other types of titrations, for example potentiometric titrations.
  7. 7.  1. Applications : Provide standard pharmacopeial methods for the assay of unformulated drugs and excipents and some formulated drugs e.g. those lack strong chromophore 2. Used for standardization of raw materials and intermediates used in drug synthesis. 3. Certain specialist titration such as Karl Fischer
  8. 8.  1. Advantages: Capable of higher degree of precision and accuracy. 2. The method are generally robust 3. Analysis can be automated 4. Cheap to do and not require specialized apparatus
  9. 9.  Limitations: 1. Non selective 2. Time consuming if not automated and require greater level of operator skill 3. Require large amount of sample 4. Reaction of standard solution should be rapid and complete 1]
  10. 10. Procedure:  A typical titration begins with a beaker or flask containing a precise volume of the titrand and a small amount of indicator placed underneath a calibrated burette containing the titrant. Small volumes of the titrant are then added to the titrand and indicator until the indicator changes, reflecting arrival at the endpoint of the titration.
  11. 11.  Depending on the endpoint desired, single drops or less than a single drop of the titrant can make the difference between a permanent and temporary change in the indicator. When the end point of the reaction is reached, the volume of reactant consumed is measured and used to calculate the concentration of analyte
  12. 12. Preparation techniques  Typical titrations require titrant and analyte to be in a liquid (solution) form. Though solids are usually dissolved into an aqueous solution, other solvents such as glacial acetic acid or ethanol are also used. [2]  Concentrated analytes are often diluted to improve accuracy.
  13. 13.  Many non-acid-base titrations require a constant pH throughout the reaction. Therefore a buffer solution may be added to the titration chamber to maintain the pH.[3]  In instances where two reactants in a sample may react with the titrant and only one is the desired analyte, a separate masking solution may be added to the reaction chamber which masks the unwanted ion.[4]
  14. 14.  Some redox reactions may require heating the sample solution and titrating while the solution is still hot to increase the reaction rate. For instance, the oxidation of some oxalate solutions requires heating to 60 °C (140 °F) to maintain a reasonable rate of reaction.[5]
  15. 15. Titration curves  A titration curve is a curve in the plane whose xcoordinate is the volume of titrant added since the beginning of the titration, and whose ycoordinate is the concentration of the analyte at the corresponding stage of the titration (in an acid-base titration, the y-coordinate is usually the pH of the solution).[6]
  16. 16.  In an acid-base titration, the titration curve reflects the strength of the corresponding acid and base. For a strong acid and a strong base, the curve will be relatively smooth and very steep near the equivalence point. Because of this, a small change in titrant volume near the equivalence point results in a large pH change and many indicators would be appropriate (e.g. phenolphthalein or bromothymol blue).
  17. 17. Strong acid and strong base curve
  18. 18.  If one reagent is a weak acid or base and the other is a strong acid or base, the titration curve is irregular and the pH shifts less with small additions of titrant near the equivalence point. For example, the titration curve for the titration between oxalic acid (a weak acid) and Na OH (a strong base), the equivalence point occurs between pH 8-10,
  19. 19.  Indicating the solution is basic at the equivalence point and an indicator such as phenolphthalein would be appropriate.  Titration curves corresponding to weak bases and strong acids are similarly behaved, with the solution being acidic at the equivalence point and indicators such as methyl orange and bromothymol blue being most appropriate.
  20. 20. Strong acid and weak base curve
  21. 21.  Titrations between a weak acid and a weak base have titration curves which are highly irregular. Because of this, no definite indicator may be appropriate and a pH meter is often used to monitor the reaction.[7]  The type of function that can be used to describe the curve is called a sigmoid function.
  22. 22. Weak acid and weak base curve
  23. 23.  Endpoint  and equivalence point Although equivalence point and endpoint are used interchangeably, they are different terms. Equivalence point is the theoretical completion of the reaction: the volume of added titrant at which the number of moles of titrant is equal to the number of moles of analyte, or some multiple thereof (as in polyprotic acids).
  24. 24.  Endpoint is what is actually measured, a physical change in the solution as determined by an indicator or an instrument mentioned above.[8]  There is a slight difference between the endpoint and the equivalence point of the titration. This error is referred to as an indicator error, and it is indeterminate.[9]
  25. 25. Types of titrations: There are many types of titrations with different procedures and goals. The most common types of quantitative titration are acid base titrations and redox titrations.
  26. 26. 1. Acid base titrations  Acid-base titrations depend on the neutralization between an acid and a base when mixed in solution. In addition to the sample, an appropriate indicator is added to the titration chamber, reflecting the pH range of the equivalence point. The acid-base indicator indicates the endpoint of the titration by changing color.
  27. 27. The following table show some indicators used with their pH ranges and colors of each : Indicator Color on acidic side Range of pH color change Color on basic side Methyl Violet Yellow 0.0–1.6 Violet Bromophenol Blue Yellow 3.0–4.6 Blue Methyl Orange Red 3.1–4.4 Yellow Methyl Red Red 4.4–6.3 Yellow Litmus Red 5.0–8.0 Blue Bromothymol Blue Yellow 6.0–7.6 Blue Phenolphthalein Colorless 8.3–10.0 Pink Alizarin Yellow Yellow 10.1–12.0 Red
  28. 28.  The endpoint and the equivalence point are not exactly the same because the equivalence point is determined by the stoichiometry of the reaction while the endpoint is just the color change from the indicator. Thus, a careful selection of the indicator will reduce the indicator error.
  29. 29.  For example, if the equivalence point is at a pH of 8.4, then the Phenolphthalein indicator would be used instead of Alizarin Yellow because phenolphthalein would reduce the indicator error  When more precise results are required, or when the reagents are a weak acid and a weak base, a pH meter or a conductance meter are used.
  30. 30. 2. Redox titration  Redox titrations are based on a reduction-oxidation reaction between an oxidizing agent and a reducing agent. A potentiometer or a redox indicator is usually used to determine the endpoint of the titration, as when one of the constituents is the oxidizing agent potassium dichromate, the color change of the solution from orange to green is not exact, therefore an indicator such as sodium diphenylamine is used.
  31. 31.  Some redox titrations do not require an indicator, due to the intense color of the constituents. For example, in permanganometry a slight faint persisting pink color signals the endpoint of the titration because of the color of the excess oxidizing agent potassium permanganate.[10]
  32. 32. 3.Gas phase titration Gas phase titrations are titrations done in the gas phase, specifically as methods for determining reactive species by reaction with an excess of some other gas, acting as the titrant. In one common the gas phase titration, gaseous ozone is titrated with nitrogen oxide according to the reaction: O3 + NO → O2 + NO2.[11][12]
  33. 33.  After the reaction is complete, the remaining titrant and product are quantified (e.g., by FT-IR); this is used to determine the amount of analyte in the original sample.
  34. 34. 4. Complexometric titration Complexometric titrations rely on the formation of a complex between the analyte and the titrant. In general, they require specialized indicators that form weak complexes with the analyte. Common examples are Eriochrome Black T for the titration of calcium and magnesium ions, and the chelating agent EDTA used to titrate metal ions in solution.[13]
  35. 35. 5. Back titration Back titration is a titration done in reverse; instead of titrating the original sample, a known excess of standard reagent is added to the solution, and the excess is titrated. A back titration is useful if the endpoint of the reverse titration is easier to identify than the endpoint of the normal titration, as with precipitation reactions.
  36. 36.  Back titrations are also useful if the reaction between the analyte and the titrant is very slow, or when the analyte is in a non-soluble solid.[16]
  37. 37. Measuring the endpoint of a titration  There are different methods to determine the endpoint include:[17] 1. Indicator: A substance that changes color in response to a chemical change. An acid-base indicator (e.g., phenolphthalein) changes color depending on the pH. Redox indicators are also used. A drop of indicator solution is added to the titration at the beginning; the endpoint has been reached when the color changes.
  38. 38. 2. Potentiometer: An instrument that measures the electrode potential of the solution. These are used for redox titrations; the potential of the working electrode will suddenly change as the endpoint is reached. The pH meter is a potentiometer with an electrode whose potential depends on the amount of H+ ion present in the solution. (This is an example of an ion-selective electrode.)
  39. 39. 3. Conductivity: A measurement of ions in a solution. Ion concentration can change significantly in a titration, which changes the conductivity. (For instance, during an acid-base titration, the H+ and OH- ions react to form neutral H2O.) As total conductance depends on all ions present in the solution and not all ions contribute equally (due to mobility and ionic strength).
  40. 40. 4. Color change: In some reactions, the solution changes color without any added indicator. This is often seen in redox titrations when the different oxidation states of the product and reactant produce different colors. 5. Spectroscopy: Used to measure the absorption of light by the solution during titration if the spectrum of the reactant, titrant or product is known. The concentration of the material can be determined by Beer's Law.
  41. 41. 6. Precipitation: If a reaction produces a solid, a precipitate will form during the titration. A classic example is the reaction between Ag+ and Cl- to form the insoluble salt AgCl. Cloudy precipitates usually make it difficult to determine the endpoint precisely. To compensate, precipitation titrations often have to be done as "back" titrations .
  42. 42. 7. Amperometry: Measures the current produced by the titration reaction as a result of the oxidation or reduction of the analyte. The endpoint is detected as a change in the current. This method is most useful when the excess titrant can be reduced, as in the titration of halides with Ag+.
  43. 43. 8. Isothermal titration calorimeter : An instrument that measures the heat produced or consumed by the reaction to determine the endpoint. Used in biochemical titrations, such as the determination of how substrates bind to enzymes.
  44. 44. 9. Thermometric titrimetry: Differentiated from calorimetric titrimetry because the heat of the reaction (as indicated by temperature rise or fall) is not used to determine the amount of analyte in the sample solution. Instead, the endpoint is determined by the rate of temperature change.