Precipitation Titrations
Learning Outcomes
• Understand the theories and principles in
using Precipitation and Volhard method
• Compute for the percentage amount of
drugs analyzed by precipitation method.
Precipitation Method of Titration
• Reaction that involved formation of relatively
insoluble substances or precipitates to complete
the reaction.
• It follows the solubility product principle
• Precipitation titrations are based upon reactions
that yield ionic compounds of limited solubility.
Precipitation Method of Titration
• End point Determination
– Cessation of precipitation or appearance of
turbidity
– Use of internal indicators
– Instrumental methods
Precipitation Method
• Standard Solutions : 0.1N silver nitrate , 0.1N
NH4SCN
• Indicators :
– Adsorption Indicators such as eosin Y T.S. TEE
(tetrabromophenolphthalein ethyl ester), and DCF
(dichlorofluorescein). – acts by attaching to the silver
chloride ion forming a change in color
– Potassium chromate (K2CrO4)- reacts with the Ag
forming red ppt of Ag2CrO4.
– Ferric ammoniun sulfate FeNH4(SO4)2 - reacts with
SCN to form Fe(SCN)3 which is red brown ppt.
Precipitation methods
• Argentometric method/Mohr method
• Direct titration with Ammonium
Thiocyanate
• Volhard method or RTM Precipitation
Argentometric Method/ Mohr
Method
Standard solution: Silver nitrate solutions
Indicator: Potassium chromate
Method: Direct Titration Method (DTM)
Analyte:
- Anticoagulant heparin solution
- Iopanoic acid
- Betazole HCl
- Lithium chloride
- Naloxone HCl
Argentometric/Mohr Method
• Theory:
Analyte (compounds containing chlorides)
reacts with AgNO3 solution forming white silver
chloride precipitates, the first excess of titrant
results in the formation of a silver chromate
precipitates, which signals the end point.
Ex. HCl + AgNO3 = AgCl + HNO3
K2CrO4 + 2AgNO3 = Ag2CrO4 + 2KNO3
Argentometric/Mohr Method
The reactions are:
Using HCl as the precipitating agent:
AgNO3 + HCl AgCl + HNO3
Using NaCl as the primary standard
AgNO3 + NaCl AgCl + NaNO3
Reaction with K2CrO4
2AgNO3 + K2CrO4 Ag2 CrO4 (red ppt)+ 2KNO3
Argentometric/Mohr Method
Formula :
% = _V x N x meq x100
wt of analyte
DTM with Ammonium
Thiocyanate (NH4SCN)
• Standard solution: NH4SCN solutions
• Indicator: Ferric ammonium sulfate
{FeNH4(SO4)2 }
• Analytes: (silver and mercuric compounds)
• - Silver nitrate
• - Mercuric sulfate
• - Nitromersol
• - Phenyl mercuric acetate
• - Silver Oxide
DTM with Ammonium
Thiocyanate (NH4SCN)
Reactions with silver and mercury (as analyte)
AgNO3 + NH4SCN AgSCN + NH4NO3
Hg(NO3)2 + 2NH4SCN Hg(SCN)2 +2NH4NO3
Reactions with the FeNH4(SO4)2 (indicator)
FeNH4(SO4)2 + 3NH4SCN Fe(SCN)3 +2(NH4)2SO4
DTM with Ammonium
Thiocyanate (NH4SCN)
Formula :
% = V x N x meq x 100
wt of analyte
Residual Titration Method
(Volhard method)
• Uses a back titration with ammonium thiocyanate to
determine the concentration of chloride ions in a
solution.
• Before the titration an excess volume of a silver nitrate
solution is added to the solution containing chloride ions,
forming a precipitate of silver chloride.
• The term ‘excess‘ is used as the moles of silver nitrate
added are known to exceed the moles of sodium
chloride present in the sample so that all the chloride
ions present will react.
• Ag+(aq) + Cl-(aq) --> AgCl(s)
Volhard Method
• The indicator Fe3+ (ferric ion) is then added and the
solution is titrated with the ammonium thiocyanate
solution. The titrate remains pale yellow as the excess
(unreacted) silver ions react with the thiocyanate ions to
form a silver thiocyanate precipitate.
• Ag+(aq) + SCN -(aq) --> AgSCN
• Once all the silver ions have reacted, the slightest
excess of thiocyanate reacts with Fe3+ to form a dark red
complex.
• Fe3+(aq) + SCN -(aq) --> Fe(SCN)3
Reactions involved in Volhard
Method
1. Reaction between the analyte and the standard
solution
NaCl + AgNO3 AgCl + NaNO3
2. Reaction between the standard solutions
AgNO3 + NH4SCN AgSCN + NH4NO3
3. Reactions with the FeNH4(SO4)2 (indicator)
FeNH4(SO4)2 + 3NH4SCN Fe(SCN)3 +2(NH4)2SO4
List of Pharmaceutical Products Assayed by
Volhard Method
• Acetylcholine chloride
• Aminophylline
• Ammonium chloride
• Ammonium bromide
• Chlorobutanol
• Povidone-Iodine
• Sodium chloride
• Theophylline
Volhard method
• The concentration of chloride ions is determined by
subtracting the titration findings of the moles of silver
ions that reacted with the thiocyanate from the total
moles of silver nitrate added to the solution.
This method is used when the pH of the solution after
the sample has been prepared is acidic.
• Formula :
(VagNO3 x NAgNO3) - (VNH4SCN x N NH4SCN ) meq
• % = _________________________________ x 100
wt of analyte
Practice Problems
• Preparation and Standardization of 0.1N
Silver Nitrate
• Data:
– Primary standard used: Sodium chloride
– Standard solution: 0.1N AgNO3
– Indicator: Eosin Y TS
– Compute for the exact Normality of Silver
nitrate solution.
Data: 0.12g of NaCl, 25 mL of AgNO3
What is the normality of AgNO3
Practice Problems
1. How much of 0.1N AgNo3 should be
prepared from 3g of pure silver? Ag = 108
Practice Problems
Calculate the weights of the following that is equivalent to 1
mL of 0.1N ammonium thiocyanate.
- Mercuric sulfate reagent (HgSO4)
- Nitromersol ( Hg(NO3)2 )
- Hg = 200.59, S- 32, N=14, O -16
Reaction:
Practice Problems
A 0.2182 g sample of sodium chloride was assayed by
Volhard method using 50mL of 0.0985N silver nitrate
and 11.75mL of 0.1340N ammonium thiocyanate.
Calculate the percent sodium chloride of the sample.
References
• Jenkins, Glenn L. et al. Jenkin’s Quatitative Pharmaceutical Chemistry, 6th
ed., USA: Mc Graw Hi:2008
• Alfonso, G. Remington: The Science and Practice of Pharmacy. 20th Ed.
Pennsylvania: Mack Publishing Company, 2006.
• Ansel, Howard, Pharmaceutical Calculations. 13th Ed. Maryland, Lippincott
Williams and Wilkins: 2010
• Ashutosh Kar, Pharmaceutical Drug Analysis, Revised 2nd Ed, India ,New
Age International, 2005
• Chatten, Leslie G., Pharmaceutical Chemistry-Theory and Application Vol.1,
India, CBS Publishers & Distributors, 2008
• Hansen, Steen, Introduction to Pharmaceutical Chemical Analysis. 1st ed. ,
John Wiley & Sons Ltd. 2012.
• United States Pharmacopoeia and National Formulary. Vol 1,2 and 3, latest
edition
• Watson, David G., Pharmaceutical Analysis. 3rd ed. Elsevier Ltd. 2012