Analytical 1 Volumetric PDF

General terms and formula used in volumetric analysis. > Concentration the concentration of a chemical substance expresses the amount ofa substance present in a mixture. It is mainly represent in the molar concentration in pharmaceutical. Concentration =Mole...

General terms and formula used in volumetric analysis. > Concentration the concentration of a chemical substance expresses the amount ofa substance present in a mixture. It is mainly represent in the molar concentration in pharmaceutical. Concentration =Moles of solute/volume in litre. Solution-- Solutions are homogeneous mixture of two or more than two components. Generally the component that is present in the large amount is known as the solvent or other; one or more components presents in the solution other than solvent are called solutes. Solvent determines the physical state in which solution is exists. Solution = solute + solvent. Mass percentage (w/w) Mass %of a component = Mass of the component in the solution_x 100 Total mass of the solution >Volume percentage (v/v) Volume % of a component = volume of the component x 100 Total volume of solution > Mass by volume percentage (m/v)-Mass of solute dissolved in 100ml of the solution. m/y = mass of solute x 100 Volume of solution > Molarity- Molarity= moles of solute X 100 Volume of solution in litre > Molality- Molality = moles of solutex 100 Mass of solvent in kg  Normality- Normality = gram equivalent of solute x 100 liters of solution > Parts per million When a solute is present in trace quantities, it is Convenient to express concentration in parts per million (ppm). PPM = number of parts of the component 100 Total number of parts of all components of the solution > Mole fraction number of moles of the component Total number of moles of all components. CHEMICAL/ Titrimetric METHODS. In the chemical analysis we discuss about the chemical reaction of the components and discuss the chemical property. It includes chemical many methods. > Volumetric analysis. > Gravimetric analysis. VOLUMETRICANALYSIS. Volumetric analysis is the method of quantitative chemical analysis in which the amounts of the substances is determined by measuring the volume that it occupies in different- different proportions. We analyte the strength, of the chemical which are involved in the chemical reaction and calculate the proportions. Trimetric methods are still widely used in the pharmaceutical analysis than geometric analysis because of their robustness, cheapness, and capability for high precision. Volumetric methods are classified into different types depending upon the types of reactions involved in the reactions which are as follows.  1. Neutralization titration. 2. Non- aqueous titration. 3. Redox titration. 4. Complex metric titration. 5. Precipitation titration. 1Neutralization(Acid-Base )Titration titration in aqueous phase. In this method strong It is also known as acid base are used as are used as titrate or analyte and other reagent or titrant acid/base concentration of analyte. standard solution to define the of determine the unknown concentration Titration- Titration is the phenomena to prepared as a identified solution or analyte. In this method, a reagent or titrant is an titrant concentration and volume of the prepared standard solution, then a known the concentration. reacts with the analyte to determine Acid base theory. ACID. substances which produce Arrhenius concept-According to this concept, those are called acids. free hydrogen ion (H) in an aqueous solution Example- HCI, HNO3, H,SO4, CH;COOH etc. which Bronsted-Lowry concept According to this concept, those substances solvent are called have tendency to donate the proton (H") by any methods in any acids. tendency Lewis concept-According to this concept, those substances which have to gain lone pair or electron pair are called acids. Example - AICIs, SF6, SO; etc.  BASE/ALKALI. Arrheniusconcept-According to this concept, those free hydroxide ion (OH) in an aqueous solution are substances which produce called bases. Example-NaOH, KOH,Ca(OH)2 ctc. Bronsted-Lowry concept-According to this concept, those substances which have tendency to accept the proton (H*) by bases. any methods in any solvent are called Example - S042, C, o² Lewis concept--According to this concept, those substances which have to donate lone pair or electron pair are called bases. tendency Types of Neutralization titration A. Strong acid/Strong base titrations-In this titration strong acid and strong base are reacted with each other by using a suitable indicators. Acid and base components are rapidly and anion) and react with each other and breakdown in its ions (cation form the salt > Titration curve is plotted on the basis of reaction between HClandandwater. 14 13 14 13 NaOH 12 12 11 11 10 10 9 pH 8 8 pH 7 6 Equivalence point 7 6 5 5 4 4 3 3 2 2 1 1 0 10 20 30 40 50 60 mL0.10OM NaOH added to 50.00mL 0.100M HCI Initially, the curve show lowPH due to the presence of strong acid which slowly rises as the base is added slowly and reaches tosharp rise after the  presence excess of end point or neutralization point to higher PH due to alkali. at which point all acid " The neutralization point occurs at PH-7 the base molecule. moleculeshave completely consume or reacts with curve will have the same NOTEAllthe strong acid and strong base shape. In weak base strong acid titrations B. Weak acid/strong base and weak titrated with the strong base or this titration method weak acid is by using the suitable indicators to base is titrated with the strong acid procedure weak acid or weak base are detect the end point. During the acid or strong base dissociates slowly in its components and strong type of titration is aredissociates rapidly in its components so this differ from previous titration method. WASB-Thahon) HEP EF H EP HEP wBSA-Tialior valum Addid > Titration curve plotted for both the titration is where " Initially the PH rises normally and when it reaches a zone reactions proceeds, the curve will not raise much. This point is said tobe half neutralization point. At this point, there is no much change in PH even though lot of strong base is added and the half of the weak acid is reacted with the base to form acid conjugate base which means there will be mix of conjugate base and solution, it is a buffer solution.  Thus the H ion concentration willbe equal to the Ka value of the weak acid [PH= PKa]. After this zone, there will be a sharp rise in PH through its equivalence point due to the excess strong alkali above PH-7. This is because, all the weak acid molecule react with the base to form the conjugate base and only the base is remaining which rise the PH and there fore the curve follows the pattern as strong acid and base titration. strong C. Weak acid-weak base titration- In this titration method weak acid and weak base titrate with each other by using the suitable indicators (mixed indicators). " The chief feature of the curve is that change of PH near equivalence point and during whole neutralization is very gradual. Hence, the end point cannot be detected by ordinary indicator. For detection of this titration mixed indicators are used. > BACK TITRATION-In case of insoluble substances which are volatile, reactions require additional heat, and substances for which reaction proceeds rapidly only in the presence of excess of reagents, direct titration willnot be possible. These substances are determined by the back titration method. The determination involves addition of excess but known quantity of the standard solution to the weighed sample of analyte and after the complete the reaction, excess of solution is back titrated with standard solution. Some important neutralization titration and their methods and titrant given below  Type of titration Titrant Standard chemical Back H,So4 |Aspirin NaOH Ammonium chloride Back Back HCI Methyl salicylate NaOH Back Ephedrine NaOH Furosemide Back NaOH Pyrazinamide Back Sodium hydroxide Direct H,So4 Direct H,So4 Theopentone sodium Direct NaOH Calamine Direct NaOH Oxyphenbutazone Direct NaOH Salicylic acid Direct NaOH Boric acid Hydrochloric acid Direct NaOH Nicotinic acid Direct NaOH Saccharin Direct NaOH  Neutralization Indicators. Indicators- Chemical indicators are those substances which give a visible or distinguishable sign, usually by acolor odor change etc of the presence or absence of a change, state change, and chemical species, such as an acid or an alkali in threshold a solution. concentration of a Neutralization indicatorsThose substances used in acid base titration that are helpful in detection of end point at the end of reaction by different color at the end point at various value of PH. So after the producing neutralization point, they produce color titrate, and thus denote the end point. change as per the PH of the titrant or Examples of indicators-Table given below Indicators PH range Acid Thymol blue Base 1.2 -2.8 Red Yellow Methyl red 4.2 -6.3 Red Yellow Methyl orange 3.1 -4.4 Red Orange Bromocresol green 3.8 - 5.4 Yellow Blue Bromocresol blue 3.0 4.6 Yellow Blue Phenol red 6.8- 8.4 Yellow Red Phenolphthalein 8.3 -11 No color Red 2.Non-aqueous Titration. Non aqueous titration is the most common titration procedure used in pharmacopoeial assays and serves a double purpose, as it is suitable for the titration of weak acids and weak bases and provides a solvent in which organic compounds are soluble  solvent used Commnon volumetric solvent-water is the most common nature, common in the volumetric titration because due to amphoteric acid or base is to availability, low cost, solubilizing capability etc. When andesired water to achieve the be used, they have to be dissolved in compounds or drugs which are concentration. However, the pharmaceutical These in various formulations are weak acidic and basic substances. used have major limitation that they a poor soluble in water and have compounds low reacting properties. acid and base is relatively weak then it will not compete effectively If the electron/proton. In other word, it will not be titrated. with water for H20 + H* H30+ RNH3+ Competes with RHN2+ H+ H20 + B OH + BH+ RO + BH+ Competes with ROH + B Titration. Solvents used in the Non- aqueous used in the non- aqueous titration. > Generally organic solventsare donor > The non-aqueous solvents can be classified based on its proton influence on the acid- base acceptor properties. The solvent exert an properties of the solute they are of four types. 1) Protogenic solvents. 2) Protophilic solvents. 3) Aprotic solvents. 4) Amphiprotic solvents. and tend to have Protogenic Solvents- these solvents have a more acidic character These solvents have a levelling effect on the bases they come in contact with. relatively high dielectric constant. They are ionized and the ionic products of librated ions are usually greater than that of water. Example- formic acid, acetic acid, sulphuric acid etc. Protophilic solvents- these arce basic in nature and reacts with acid to form the Solvated proton. It shows the greater tendency to the accepting the proton and high dielectric constant. have They are ionized and the ionic product is less than ionic products of the water. Example- imethyl formaldehyde, pyridine, ammonia etc. Aprotic solvents-- these solvents are generally hydrocarbons or chlorinated hydrocarbons. Thesechemically solvents neutral and not contain any protons or hydrogen containing bonds refers as the 0-H or N-H bonds. These solvents posses low dielectric constant and they are generally not ionized o give ion. Example- Benzene, acetone, chloroform etc. Amphiprotic solvents-- these solvents posses both acidic and basic high dielectric constant. properties and They are partially ionized and the ionic products of librated jons is less than that of water. Example- water, ethanol, isopropyl alcohol etc. Types of Non-agueous titration A. Non-aqueous titration of weak base- Acetic acid is a very weak proton acceptor and thus does not compete efectively with weak base for proton only very strong acids will protonate acidic acid appreciably according to the equation shown below CH;COOH + HA CH,C0OH;* + A In this titration method weak bases compete very effectively with acetic acid for protons. Non-aqueous titration with acetous perchloric acid is used in the pharmacopoeial assays of adrenaline, metronidazole, codeine, amitriptyline HCI, Lignocaine HCI, Quaternary amine salts such as Neostigmine bromide, and pancuronium bromide. > Oracet blue, quinolidine red and crystal violet are used as indicator in this type of titration.  B. Non-aqueous titration of weak acid- for Non-aqueous titration of weak acids a solvent such as an alcohol or an aprotic solvent is used that does not compete strongly with the weak acid for proton donation. Typical titrants are lithium methoxide in methanol or tetrabutyl ammonium hydroxide in dimethyl formamide. pharmacopoeial NOn- aqueous titration of acidicgroups is carried out in assays of barbiturates, uracils, and sulphonamides. blue as an For the end point detection may be carried out with thymol indicator. Redox titration. reduction reaction is employ is Chemical titration in which both the oxidation - titration. known as Redox titration or oxidation -reduction as 'addition ofoxygen/loss of Oxidation reaction-Oxidation reaction is defined electron/removal ofhydrogen' is known as oxidation reaction. 'removal of oxygen/gain of Reduction reaction--Reduction reaction is defined as reaction. electron/addition of hydrogen' is known as oxidation MnO4 + I Mn + I2 Redox reaction- substances containing an Oxidizing agent- Oxidizing agent are defined as result in either decrease atom/ion, which accept an electron during the reaction and valency. in their positive valency or increase in their negative containing an Reducing agentReducing agent are defined as substances either increase atom/ion, which loose an electron during the reaction and result in of their positive valency or decrease of their negative valency. Theory on redox titration-Reduction potential is a measure of how thermodynamically favorable it is for a compound to gain electrons. Ahigh positive value for a reduction potential indicates that a compound is readily reduced and consequently is a strong oxidizing agent that is it removes electrons from substances with lower reduction potential. The oxidized and reduced forms of a substance are known as a redox pair. Some standard redox potential (Eo) given in the table- Ce+ t e ’ Ce3+ 1.61v Mnt Mn't 1.51v Cl, + 2e ’ 2C1 1.36v BrT + 2e ’ 2Br 1.065v Fet + Fe2t 0.771y + 2e ’ 21 0.536v AgCl t e ’ Ag + CI 0.223v 2H + 2e H Ov Fe2t + 2e ’ Fe -0,440v Ca't + 2e Ca - 2.888v Asubstance with a higher reduction potential will oxidize one with a lower reduction potential. Example- Ch t 2Br ’ 2C1 + Br,. Direct Redox Titration- lodine is a moderately strong oxidizing agent. During oxidation it will oxidize substances with lower reduction potential. Example titration of ascorbic acid. In addition the end point is detected using starch indicator, which produces a blue coloration with excess iodine. The pharmacopoeial assays of this titration are ascorbic acid, sodium stilbigluconate, dimercapral injection and acetarsal. Displacement redox titration- this titration is used in the pharmacopoeial assays of- liquefied phenol, Methyl hydroxybenzoate, Propyl hydroxybenzoate and phenidione. Complex metric titration. This type of titration involves formation of complex during the titration and is used in the estimation of metal and also for their salts. The titrant used in this titration is