Titrimetric analysis

Titrimetric analysis is a method of analysis in which a solution of the substance being determined is treated with a solution of a suitable reagent of exactly known concentration. The reagent is added to the substance until the amount added is equivalent to the amount of substance to be determined.

1. TITRIMETRIC ANA L Y SIS MS. KAD DHANASHREE R. ASSISTANT PROF. P’CAL CHEMISTRY PES MODERN COLLEGE OF PHARMACY (FOR LADIES), MOSHI,PUNE

2. Introduction Volumetric analysis deals with the measurement of volume of solutions involved in the chemical reactions which ultimately lead to the determination of the amount of the constituents of the substance. 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. Pharmaceutical analysis is the quantitative measurement of the active ingredient and related compounds in the pharmaceutical product These determinations require the highest accuracy, precision, and reliability because of the intended use of the data as in: Manufacturing control (identify drug in formulation),

4. Stability evaluation (determine the impurity and degradation products in the stability study), and shelf-life prediction. 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.  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. Different ways of expressing the concentration of the solutions The amount of the substance present in the definite quantity of the solution is called concentration of the solutions. There are many ways of expressing the concentration of the solution. The concentration of the solution can be expressed in any of the following ways. 1.Gram per litre: The amount of the solute in gram present in one litre of the solution is known as gram per litre of the solution . Eg . If 5 gram of NaOH is dissolved in 500 ml of the solution then its strength is 10 g/l.

7. Normality : The number of gram equivalent of solute present in a litre of the solution is known as normality of the solution. Normal solution(1 N) Seminormal solution (N/2) Decinormal solution (N/10) Centinormal solution ( N/100) Pentanormal solution ( 5N) Decanormal solution (10N) M o l a r i t y : The number of the moles of solute present in a litre of the solutions is known as molarity of the solutions

8. Percentage(%): Percentage strength means number of parts of solute in 100 parts of solution which is expressed in three different ways: % in weight by weight (w/W): it may be defined as the amount of solute in gram present in 100 gram of the solution. Simply, % by w/W =( wt of solute in gm/wt of the solution in gm) ×100% % in weight by volume (w/V): it may be defined as the amount of solute in gram present in 100 ml of the solution. Simlpy, % by w/V =( wt of solute in gm/volume of the solution in ml ) × 100% c. % in volume by volume (v/V): it may be defined as the volume of solute in ml present in 100 ml of the solution. Simply, % by v/V =( volume of solute in ml/volume of the solution in ml) × 100 %

9. M o l a l i t y : The number of the moles of solute present in one kg of solvent is known as molality of the solution. Molality = ( no. of moles of solute )/ (wt of solvent in Kg) Some terms related and terminology related to volumetric analysis Unknown solution : The solution whose strength is not known i.e. the solution whose strength is to be determined during the titration is known as unknown solution. Standard solution : The solution whose strength is known is known as standard solution.

10. Titration: The process in which the concentration of unknown solution is determined with the help of standard solution by using the indicator is called titration. Titrant The solution of known concentration which is usually taken in a burette is called titrant . Titrand : The solution of unknown concentration which is being titrated and usually taken in a conical flask is called titrand . End point: The point in a titration at which reaction between two solution is just completed and at which indicator can show sharp colour change is called end point .

11. Equivalence point or theoretical point: The stage during the titration at which exactly equivalent amount of titrant is added to titrand is known as equivalence point . In theoretical concept, when equivalent amount of titrant is added to the titrand, the indicator should change the colour and indicate the end point. But in actual practice, the indicator doesn’t change its colour at equivalence point. This is because the indicator changes its colour either in acidic or alkaline medium. Therefore in practice a small difference occurs between equivalence point and end point. This difference in titration is known as titration error .

12. Primary standard substance : The substance whose standard solution can be prepared directly by dissolving the known weight of the substance in fixed volume the solution is known as primary standard substance. E.g. anhydrous sodium carbonate, oxalic acid, silver nitrate etc. The solution of primary standard substance is known as primary standard solution. Requirements for a substance to be primary standard It must be available in pure form and should be non toxic. It should not be hygroscopic( ability to absorb moisture) or deliquescent(turns to solution). It should have high molecular weight or equivalent weight so as to minimise the weighing error during weights. It should be readily dissolve in water. It should be stable. In other words, the composition of substance should not change in solid or in solution state for long time.

13. Secondary standard substance: The substance whose solution can be standardise or strength can be determined by the help of primary standard solution is known as secondary standard substance and the solution is known as secondary standard solution. Eg. NaOH, HCl, KMnO 4 , FeSO 4 . Normality factor: It is defined as the ratio of actual weight of the substance taken to the theoretical weight of the substance to be taken and usually denoted by “ f ”.

14. Applications Provide standard pharmacopeial methods for the assay of unformulated drugs and excipents and some formulated drugs e.g. those lack strong chromophore Used for standardization of raw materials and intermediates used in drug synthesis. Certain specialist titration such as Karl Fischer

15. Advantages Capable of higher degree of precision and accuracy. The method are generally robust Analysis can be automated Cheap to do and not require specialized apparatus

16. Limitations Non selective Time consuming if not automated and require greater level of operator skill Require large amount of sample Reaction of standard solution should be rapid and complete 1]

17. Titration curves  A titration curve is a curve in the plane whose x - coordinate is the volume of titrant added since the beginning of the titration, and whose y - coordinate 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 ).

18. 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.

19. 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.

20. 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 The following table show some indicators used with their pH ranges and colors of each :

21. 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.

22.  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 permangana te .

23. 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 .

24. 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.

25. There are different methods to determine the endpoint include : 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.

26. 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.)

27. 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 H 2 O.) As total conductance depends on all ions present in the solution and not all ions contribute equally (due to mobility and ionic strength).

28. 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. 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.

29. 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 .

30. 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 + .

31. 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.

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