Pharmaceutical Analysis

Transcription

1 Pharmaceutical Analysis 62 Pharmaceutical Analysis Definition: Chemical Analysis is a method for determining the substance, its amount or impurity and plays a vital role in the pharmacy. Analytical chemistry Methods 1. Qualitative analysis 2. Quantitative analysis Qualitative or physical analysis Recognition of chemical species by means of: Colour, taste, Viscosity and solubility Reaction producing a colour Reaction producing a precipitate Reaction involving a change of a physical parameter. Quantitative chemical analysis Quantitative chemical analysis carried out by determining the volume of a solution of accurately known concentration which is required to react quantitatively with a measured volume of the substance to be determined. Classification 1. Neutralisation Reactions 2. Complex Formation Reactions 3. Redox Reactions 4. Precipitation Reactions Basics and definitions A solution: Is a homogeneous mixture composed of two or more substances. In such a mixture, a solute is dissolved in another substance, known as a solvent.

2 Pharmaceutical Analysis 63 Concentrations: Is a measure how much of given substance there is mixed with another substance most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in a substance. Standard solution: Is a chemical term which describes a solution of known concentration. The concentration of the solution is normally expressed in units of moles per Liter (mol/l, often abbreviated to M for morality). Standard solutions are normally used in titrations to determine the concentration of a substance in solution. A molar solution: Is one that contains one mole of solute (molecular weight) per liter of solution. For example: A five molar solution of aqueous hydrochloric acid (written as "5M HCl (aq)") means there are 5 moles of HCl per liter of solution If one liter of a solution contain 98 g of H 2 SO 4, this means that the concentration is 1M If one liter of a solution contain 98x2 (196) g of H 2 SO 4, this means that the concentration is 2M Normal solution: Is one that contains one equivalent weights of solute per liter of solution. For example: A five normal solution of aqueous hydrochloric acid (written as "5N HCl (aq)") means there are 5 equivalents of HCl per liter of solution number of equivalent weights of solute no.eq Normality = = = liter of solution L no. meq ml Calculation of equivalents: 1. For acids: One equivalent of an acid is that amount of an acid that will furnish one mole of hydrogen ions or that will react with one mole of hydroxide ions.

3 Pharmaceutical Analysis 64 Example: the molecular weight of HCL is 36.5 g and contain one mole of hydrogen ions that will react with one mole of hydroxide ions: The equivalent weights of HCL is 36.5/1 = 36.5 The molecular weight of H 2 SO 4 is 98 and contain two mole of hydrogen ions that will react with one mole of hydroxide ions: The equivalent weights of H 2 SO 4 is 98/2 = 49 The molecular weight To calculate the equivalent weights of acid = Number of H ions 2. For bases: one equivalent of a base is that amount of a base that will furnish one mole of hydroxide ions or react with one mole of hydrogen ions. The molecular weight To calculate the equivalent weights of base = number of OH ions Example: NaOH + HCL NaCL + H 2 O The molecular weight of NaOH is 40 and contain one mole of hydroxide ions that will react with one mole of hydrogen ions: The equivalent weights of NaOH is 40/1 = 40 Al(OH) 3 + 3HCL ALCL 3 + H 2 O The molecular weight of Al(OH) 3 is 87 and contain three mole of hydroxide ions that will react with three mole of hydrogen ions: The equivalent weights of Al(OH) 3 is 78/3 = For Salts: one equivalent of a salt is that amount of a Salt that will result from replacement of one mole of hydrogen ions of conjugated acid. NaOH + HCL NaCL + H 2 O The molecular weight of NaCL is 58.5 and result from replacement of one mole of hydrogen ions of conjugated acid HCL. The equivalent weights of NaCL is 85.5/1 = 85.5

4 Pharmaceutical Analysis 65 H 2 CO 3 HCO H + The molecular weight of NaHCO 3 is 84 and result from replacement of one mole of hydrogen ions of conjugated acid H 2 CO 3 The equivalent weights of NaCL is 84/1 = 84 Na 2 CO 3 : The molecular weight of Na 2 CO 3 is 106 and result from replacement of two moles of hydrogen ions of conjugated acid H 2 CO 3 The equivalent weights of NaCL is 106/2 = Neutralisation Titrations (acid - base titration) Acid base titration terminology: Titration A process in which a solution of one reactant, the titrant, is carefully added to a solution of another reactant, and the volume of titrant required for complete reaction is measured. Equivalence point The point at which stoichiometrically equivalent amounts of an acid and base have reacted. Indicator A compound that exhibits its different colors in solutions of different acidities. Used to determine the point at which an acid-base reaction is complete. (phenolphthalein) End point The point at which an indicator changes color and a titration is stopped. The end point should coincide with the equivalence point Acid base titration The neutralisation reactions between acids and bases used in chemical analysis. These reactions involve the combination of hydrogen and hydroxide ions to form water. Ex: NaOH + HCL NaCL + H 2 O

5 Pharmaceutical Analysis 66 To perform neutralisation titration is necessary to have a solution of base for example at known concentration a glass vessel, a burette (calibrated tube able to measure volume, equipped with a tap) and an indicator (chemical species able to change colour when change the composition of the solution. Change of ph The standard solution for the titration must be strong base or acid (for complete dissociation and reaction) Weak acids and bases dissociate and react partially so can not be used by titration as standard reagent. Ex: NH 4 OH + HCL NH 4 CL + H 2 O NH 4 OH dissociates partially in a solution into (NH 4 OH NH H 2 O). Thus by titration ammonia ions will be not consumed by reaction with HCL and still free. Color change of the indicator will appear only if the whole chloride ions are consumed. Requirements of standard reagents: 1. Not volatile and stable 2. Complete dissociation and ionization

6 Pharmaceutical Analysis Have no oxidation properties (to prevent oxidation of indicator) 4. Are not insoluble salts because this make detection of end point difficult. Types of acid- base titration: 1. Non-Aqueous Take place in a solvent other than water (Glycerin, Polyethelene glycol, alcohol) Used for weak substances which dissociate partially in water making difficulties in determining change of ph Called non aqueous titration Ex: CH3COOH CH3COO - + H + 2. Aqueous Take place in water Used for substances which dissociate completely and rapidly in water Determination of change of ph is easy Called aqueous titration Requirements of indicators: 1. The change of color is at equivalent point is clear 2. Not volatile 3. Chemically inert 4. Do not form insoluble complexes ph Indicators 1. are organic dyes with either acid or basic character 2. are organic dyes that change their colour on acceptance or release of protons 3. are used for rapid determination of an endpoint in an acid-base titration 4. are used for the quantitative determination of a given acid or base content of a solution 5. does not change the colour immediately but continuously within a given ph range Application of acid base titrations in pharmacy : Salicylic acid Benzoic acid

7 Pharmaceutical Analysis 68 General law used in calculations of neutralization titrations: No. of equivalents in a solution = Volume of the solution x Normality No. of eq. = V x N Example: NaOH Solution, Volume = 200 ml, concentration = 0.1 N Calculate the weight of NaOH in the solution? No. of eq. = V x N No. of eq. = 200/ 1000 x 0.1 = 0.02 Equivalents 1 Equivalent 40 g 0.02 Equivalents Xg Xg = (40 x 0.02)/ 1 = 0.8 g

8 Pharmaceutical Analysis Precipitation Titrations Titrations between analytes and reagents resulting in the formation of a precipitate. The most useful of these precipitating reagents is silver nitrate AgNO 3. Titrimetric methods based upon the use of silver nitrate are sometimes called Argentometric titrations. Used for the determination of many anions including: 1. Halides: Br -, CL -, I - 2. Divalent anions S 2-3. Mercaptans CH 3 SH 4. Certain fatty acids Ex: HCL + AgNO 3 AgCL + HNO 3 The precipitate will begin to form as the reaction take place and the end point will be determined at the end of reaction (after completion of precipitate) Endpoint determination is by coloured indicators (usually back titrations) or turbidity methods. Examples of solutions used in precipitation titrations 1. Silver nitrate AgNO 3 : For titration of Br -, CL -, I - and CN - HCL + AgNO 3 AgCL + HNO 3 2. Potassium thiocyanate KSCN: For titration of Ag + as AgSCN and Hg 2+ as Hg(SCN) 2 KSCN + Ag + AgSCN KSCN + Hg2 + Hg(SCN) 2 3. Potassium cyanate KCN: For titration of Copper Cu and Nickel Ni 4. Hg(NO3) 2 Mercury(II) nitrate: For titration of Copper Cl -, Br -, I -, SCN -

9 Pharmaceutical Analysis 70 Methods used for determination of equivalence point in precipitation titrations: 1. Mohr method The chromate ion is employed as an indicator in the Mohr method. Sodium chromate can serve as an indicator for the argentometric titrations of chlorine, bromine and cyanide ions, by reacting with silver to form silver chromate (Ag 2 CrO 4 ). Red Ag 2 CrO4(s) precipitates when excess Ag + rapidly increases near equivalence and thus is a useful indicator. The Mohr method will follow these reactions: Ag + + Cl - AgCl (s) white 2Ag + + CrO 4-2 Ag 2 CrO 4 (s) red 2. Volhard method The indicator used in the Volhard method is Iron(III) ion In this method, silver ions are titrated with a standard solution of thiocyanate ion, where Fe 3+ serves as the indicator imparting a red color to the solution. The most important application of the Volhard method is for determing the presence of halide ions. An excess of silver nitrate is added to the sample and back-titrated with a standard thiocyanate solution. The reaction that accompany the Volhard method are: Ag + + Cl - AgCl (s) white SCN - + Ag + AgSCN (s) white Fe 3+ + SCN - Fe(SCN) 2+ red 3. Fajans method: The indicator used in the Fajans method is Flourescein (an adsorption indicator) An adsorption indicator is an organic compound that tends to be adsorbed onto the surface of the solid in a precipitation titration. In the ideal scenario, the adsorption occurs near the equivalence point and results in a color change. The endpoint is noted by a change in color from fluorescent green to light pink.

10 Pharmaceutical Analysis 71 Flourescein structure Application of precipitation titration used in pharmacy: Determination of presence of metals in some solutions or some pharmaceutical dosage forms 3. Complexometric Titrations Def.: Titrations between cations and complex forming reagents The most useful of these complexing agents are organic compounds with several electron donor groups that can form multiple covalent bonds with metal ions Complexometric methods have been around for more than a century Rapid expansion in the 1940 s based on CHELATES. A chelate is produced when a metal ion coordinates to two or more donor groups within a single ligand. Example: Ethylenediaminetetraacetic Acid EDTA HOOCCH 2 HOOCCH 2 N CH 2 CH 2 N CH 2 COOH CH 2 COOH EDTA can complex a large number of metal ions. Approximately 40 cations can be determined by direct titration. EDTA is usually used as the disodium salt, Na 2 H 2 EDTA H 2 EDTA 2- + M 2+ [M(EDTA)] H +

11 Pharmaceutical Analysis 72 Because EDTA complexes most cations, the reagent might appear at first glance to be totally lacking in selectivity However, great control can be acheived by ph regulation and the selection of suitable indicators Indicators in complexometric titrations: Are organic complexe builders Build specific coloured metal ion complexes Used for detection of equivalent point in complexometry Typical indicators are: - Murexide - Solochrome black - Calmagite - Bromopyrogallol red - Xylenol orange

12 Pharmaceutical Analysis 73 Typical applications: 1. Determination of cations 2. Hardness of water 4. Oxidation-Reduction Titration An oxidation occurs when an atom or ion loses electrons A reduction occurs when an atom or ion gains electrons Example: Potassium Permanganate: MnO H + + 5e - Mn H 2 O (reduction) x 2 Iodine: 2I - I 2 + 2e - (oxidation) x 5 2MnO H I - 2Mn H 2 O + 2I 2 Indicators in Redox titrations:

13 Pharmaceutical Analysis 74 Typical applications: 1. Pharmaceuticals - Vitamin C determination 2. Determination of amount of iron in its raw material 3. Iodine determination Instrumental Analysis 1. Spectrophotometer 2. Fluorescence 3. Flame photometer 4. Atomic absorption 5. Electrophoresis 6. Infra red 7. Polarometer 8. Mass Spectroscopy 9. TLC (Thin layer chromatography) 10. GC (gas chromatography) 11. HPLC (High performance liquid chromatography)