1) Precipitation and complexation methods can be used for pharmaceutical analysis. Precipitation involves forming an insoluble precipitate through a reaction between the analyte and titrant. Complexation (such as EDTA titration) involves forming a stable, soluble complex between a metal ion analyte and ligand such as EDTA.
2) Key aspects of precipitation and complexation methods discussed include using indicators to determine the endpoint, factors that influence EDTA titration success, and techniques like direct and residual/back titration.
3) Examples provided include analyzing sodium chloride by Volhard or Fajan's method using indicators like eosin Y, and determining metals like calcium and magnesium through direct EDTA
1) Precipitation and complexation methods can be used for pharmaceutical analysis. Precipitation involves forming an insoluble precipitate through a reaction between the analyte and titrant. Complexation (such as EDTA titration) involves forming a stable, soluble complex between a metal ion analyte and ligand such as EDTA.
2) Key aspects of precipitation and complexation methods discussed include using indicators to determine the endpoint, factors that influence EDTA titration success, and techniques like direct and residual/back titration.
3) Examples provided include analyzing sodium chloride by Volhard or Fajan's method using indicators like eosin Y, and determining metals like calcium and magnesium through direct EDTA
1) Precipitation and complexation methods can be used for pharmaceutical analysis. Precipitation involves forming an insoluble precipitate through a reaction between the analyte and titrant. Complexation (such as EDTA titration) involves forming a stable, soluble complex between a metal ion analyte and ligand such as EDTA.
2) Key aspects of precipitation and complexation methods discussed include using indicators to determine the endpoint, factors that influence EDTA titration success, and techniques like direct and residual/back titration.
3) Examples provided include analyzing sodium chloride by Volhard or Fajan's method using indicators like eosin Y, and determining metals like calcium and magnesium through direct EDTA
1) Precipitation and complexation methods can be used for pharmaceutical analysis. Precipitation involves forming an insoluble precipitate through a reaction between the analyte and titrant. Complexation (such as EDTA titration) involves forming a stable, soluble complex between a metal ion analyte and ligand such as EDTA.
2) Key aspects of precipitation and complexation methods discussed include using indicators to determine the endpoint, factors that influence EDTA titration success, and techniques like direct and residual/back titration.
3) Examples provided include analyzing sodium chloride by Volhard or Fajan's method using indicators like eosin Y, and determining metals like calcium and magnesium through direct EDTA
PRECIPITATION AND COMPLEXATION METHODS OF PHARMACEUTICAL
ANALYSIS ANALYSIS 1 Dean Perlita M. Crucis, RPh, MSPharm || Midterms LECTURE Transcribers: Angeles
Volumetric Precipitimetry c) Tetrabromophenolphthalein ethyl ester TS
• DETERMINATION OF THE END POINT (TEE) • The end point of a reaction in analysis by 3. Mohr Method precipitation methods may be determined in • Titrant: 0.1 N AgNO3 VS the following ways: • Uses potassium chromate TS (K2CrO4) 1. Cessation of precipitation or the appearance o It forms a red precipitate of silver of turbidity chromate which is seen against the 2. Use of internal indicators background of white silver chloride. 3. Instrumental methods, i.e. potentiometer (by using pH meter) or amperometric Standard Solutions • N AgNO3 VS Precipitation • 0.1 N NH4SCN VS • As with other types of reactions, the formation of a precipitate can be used as the basis of a Direct Titration Method titration. • compounds of silver and mercury that can be • Analyte + titrant → precipitate readily converted in to soluble mercury of • The approach assumes that under the silver salts, may be estimated by direct experimental conditions used, the product is titration with standard ammonium virtually insoluble. thiocyanate solution, using ferric ammonium sulfate as indicator The equivalence point Residual Titration Method (Volhard Method) • The point where sufficient titrant has been added to be stoichiometrically equivalent to • is based on the complete precipitation of the amount of analyte. insoluble silver salts from nitric acid solution by the addition of excess standard silver • Just enough titrant has been added to react nitrate solution to a soluble salt, and the with all of our analyte. determination of the amount of silver nitrate o Now, either the amount of Cl- or Ag+ solution in excess by residual titration with is in excess. standard ammonium thiocyanate solution, o At this point, [Cl-] = [Ag+] using ferric ammonium sulfate as the indicator. Three (3) indicator methods applied to the titration of Cl- with AgNO3: • Substances other than chlorides that produce 1. Volhard Method slightly soluble silver salts are bromides, iodides, cyanides, thiocyanate, sulfides, • Formation of soluble colored complex at the phosphates, arsenate, carbonates, etc. end point • Indirect method for chloride determination • Titrant: 0.1 N AgNO3 VS and 0.1 N NH4SCN VS • Indicator: Ferric ammonium sulfate TS [Fe(NH4)(SO4)2] 2. Fajan’s Method
• Adsorption of a colored indicator at the end
point • Titrant: 0.1 N AgNO3 VS
Adsorption Indicators Assay of Sodium Chloride
a) Dichlorofluorescein TS (DCF) • USP Requirement: 99% - 100.5% b) Tetrabromofluorescein TS (Eosin Y) PRECIPITATION AND COMPLEXATION METHODS OF PHARMACEUTICAL ANALYSIS ANALYSIS 1 Dean Perlita M. Crucis, RPh, MSPharm || Midterms LECTURE Transcribers: Angeles
• Can be analyzed using either Fajans Method Complexometric Titration
or Volhard Method. • The formation of a stable, soluble complex is • Indicators: the driving force in the reaction. o FAS TS – Volhard Method • The equilibrium constant for the reaction of a o Eosin Y TS – Fajans Method metal ion with a ligand is called Kf or stability constant. • For successful titration with EDTA, Kf must be greater than 8
Factors Influencing EDTA Titration
• Activity of the metal ion • The pH at which the titration is run Complexometric/EDTA Titrations • Presence of interfering ions • a volumetric procedure for metal • Organic solvents – increases the stability of determination employing metal-ion indicators the complex in the same manner that pH indicators are • NaCl – decreases the stability of the complex used in acid-base titrations. • With the introduction of the analytical reagent Indicators disodium ethylenediaminetetraacetate, • Metal ion indicators are compounds whose a.k.a EDTA complexometric titration involved. color changes when they bind to a metal ion. Useful indicators must bind metal less strongly than EDTA does.
MgIn + EDTA → MgEDTA + In
Red colorless colorless blue
Metal Ion indicators
• Azodyes • Phthaleins • Tripheylmethanedyes • Xylenolorange • Hydroxynaphtholblue • Hydrocathecholviolet • EriochromeblackTS- the colored forms are red (pK6.3), blue (pK 11.6), yellow orange. Reagent • Disodium salt- preferred over the free acid in Color of Metal-ion Complex preparing the standard solution of EDTA. • Calmagite – wine red • EDTA (C10H14N2Na2O8 with 2H2O)- has a • Murexid – yellow (Co+2,Ni,+2,Cu+2); Red molecular weight of 372.2 (Ca+2) • The water should be metal-free, therefore • Xylenol (zyleenol) - orange – red glass-distilled water is preferred. • Pyrocatecol violet – blue • Solutions are best stored in polyethylene containers or in glass containers previously EDTA Titration Techniques prepared by boiling the container in an • Direct Titration alkaline 2% solution of EDTA to remove any o Ca 2+, Mg 2+, Zn 2+ - metal ions metal ions. which are determined by direct titration with EDTA Preparation and Standardization of 0.05 M EDTA • Residual/Back Titration • Hydroxynaphthol blue – indicator used, end o applied to the analysis of aluminum point of blue color. and bismuth compounds, since • Hydrochloric acid – solubilizes the calcium conditions for direct titration may carbonate by converting it to calcium chloride. introduce errors because of the • Sodium Hydroxide – alkalinizes the solution precipitation of the metal as to a pH of about 13, so that the Ca-EDTA hydroxides in alkaline media. complex would be stable and any magnesium o Bismuth – forms a highly stable which might be present as a contaminant complex and can be titrated at a pH would not react. as low as 1 or 2 • Displacement Method PRECIPITATION AND COMPLEXATION METHODS OF PHARMACEUTICAL ANALYSIS ANALYSIS 1 Dean Perlita M. Crucis, RPh, MSPharm || Midterms LECTURE Transcribers: Angeles
o For metals that do not give
satisfactory end point • Indirect Titration o An ion that precipitates with certain metal ions (with EDTA)
Masking • used to indicate the determination of a metal in the presence of another metal. • Can be accomplished by adjusting the solution a pH of the titration medium so that it will be favorable for complexation of the metal being determined and not of the other metal
Demasking Agent • Releases metal ion from masking agent (e.g. formaldehyde) • Cyanide complex can be demasked with formaldehyde
Auxiliary Complexing Agent
• Also serve as a masking agents. • Prevent the precipitation of the metal ion in the absence of EDTA. • Examples: ammonia, tartrate, citrate, and triethanolamine
