Pharmaceutical Analysis 1 Midterms University of Negros Occidental - Recoletos
(Quantitative Pharmaceutical Chemistry)
PRECIPITATION METHODS OF ANALYSIS Formula:
Determination of the End Point
1. Cessation of precipitation or appearance of
turbidity Fajans Method (Direct Titration Method)
2. Use of internal indicators • Adsorption indicator method
3. Instrumental methods – amperometry, • Endpoint reaction occurs on the surface of the AgCl
potentiometry, etc. precipitate
• Adsorption of a colored indicator at the endpoint
As with other types of reactions, the formation of a
• Titrant: 0.1 N AgNO3 VS
precipitate can be used as the basis of a titration:
• Adsorption Indicators:
o Dichlorofluorescein TS (DCF)
analyte + titrant ---> precipitate
o Tetrabromofluorescein TS (Eosin Y)
o Tetrabromophenolphthalein ethyl ester TS
The approach assumes that under the experimental
(TEE)
conditions used, the product is virtually insoluble.
• Relies on the change in the primary adsorbed ion
which occurs when titration goes past the
The Equivalence Point
equivalence point.
• The point where sufficient titrant has been added to
be stoichiometrically equivalent to the amount of
Mohr Method (Direct Method using K2CrO4)
analyte.
• Potassium chromate forms a red ppt seen against a
• Just enough titrant has been added to react with all
background of white AgCl
of our analyte.
• Relies on the Ksp differences of silver chloride and
silver chromate
Indicators used in official volumetric assays
• Titrant: 0.1 N AgNO3 VS
Indicators Preparati Use Endpoint
• Uses potassium chromate TS (K2CrO4)
on
o It forms a red precipitate of silver chromate
Ferric 8g FAS to Direct and Red color
which is seen against the background of
ammonium 100mL Residual endpoint
white silver chloride
sulfate (FAS) water titrations
• Standard solutions:
Potassium 10g Mohr Red ppt of
o 0.1 N AgNO3 VS
chromate TS K2CrO4 to titrations silver chromate
o 0.1 N NH4SCN VS
100mL
water
Volhard Method (Residual Titration Methods)
Adsorption Various Analyses of DCF TS
• Method is based on the complete precipitation of
indicators halides by Eosin Y TS
insoluble silver salts from HNO3 solution by addition
direct TEE TS
of excess AgNO3 to a soluble salt and determination
titration
of amount of silver nitrate solution by excess
with AgNO3
residual titration with standard NH4SCN solution.
• Formation of soluble colored complex at the
Standard Solutions used in Official Assays
endpoint
1. 0.1N Silver Nitrate (AgNO3)
• Indirect method for chloride determination
Preparation:
• Titrant: 0.1 N AgNO3 VS and 0.1 N NH4SCN VS
Molecular Wt. 169.87g/mol
• Indicator: Ferric ammonium sulfate TS
Primary Standard NaCl
[Fe(NH4)(SO4)2]
Formula:
• Steps:
o Excess Ag+ is added to the sample
o AgCl is removed via filtration
o Excess Ag+ is titrated with SCN-
2. 0.1N Ammonium thiocyanate (NH4SCN) o Fe3+ acts as an indicator forming a complex
Molecular Wt. 76.14g/mol with SCN-, after all Ag ions has been
Secondary Standard 0.1N AgNO3 consumed.
Indicator FAS
Pharmaceutical Analysis 1 Midterms University of Negros Occidental - Recoletos
(Quantitative Pharmaceutical Chemistry)
Assay of NaCl • Hydroxynaphthol blue – indicator
• Official Requirement is 99 – 100.5% • Blue – endpoint
• Can be analyzed using either Fajans Method or
Volhard Formula for Molarity of Disodium EDTA
• Indicators:
o FAS TS – Volhard method
o Eosin Y TS – Fajans method
Assay of Calcium Carbonate (CaCO3) Tablets
COMPLEXATION METHODS OF ANALYSIS
Formula for % Purity of CaCO3
Complex – resulting compound formed when a metal ion
combines with a molecule which can donate electrons
Chelate – Resulting complex formed if the combining • Blue solution – endpoint
molecules containing two or more groups that donate • 6.8071 – titer
electrons
Ligand – A molecule which provides groups for attachment to EDTA Titration Techniques
metal ions • Direct
• In add EDTA complexation reactions, the ratio of the • Residual
EDTA to the metal ion is 1:1 • Displacement
• The four oxygen and two nitrogen atoms of the EDTA • Indirect
molecule capable of entering a complexation
reaction with a metal ion makes it a hexadentate Masking and Masking Agents
molecule • Masking is a term used to indicate the determination
• For successful titrations with EDTA. The stability of a metal in the presence of another metal
constants of the complex formed must be greater • Accomplished by adjusting the pH of the titration
than 8 medium
Indications in EDTA Titrations Sample Problem
• The most common way to detect end point in EDTA • An EDTA solution is standardized against high-purity
titrations is with a metal ion indicator. CaCO3 by dissolving 0.3982 g CaCO3 in hydrochloric
• Metal ion indicators are compounds which change acid, adjusting the pH to 10 with ammoniacal buffer,
color when they bind to a metal ion and titrating. If 38.26 mL was required for the
• Metal Ion Indicators: Azo dyes, phthaleins, titration, what is the molarity of the EDTA?
triphenylmethane dyes, xylenol orange, • A 50.0 mL aliquot of solution containing 0.450 g of
hydrocathechol violet, Eriochrome back T MgSO4 (MW=120.37) in 0.500 L required 37.5 mL of
• Color of the metal ion complex: EDTA solution for titration. How many milligrams of
o Calmagite – wine red CaCO3 (MW=100.09) will react with 1.00 mL of this
o Murexide (yellow – Co, Ni, Cu; red – EDTA solution?
o Ca)
o Xylenol orange – red
o Pyrocatechol violet - blue Residual Titration Methods in Complexometry
• Qualities of the indicator: • Applies to the analysis of aluminum and bismuth
o Sharpness of color change compounds
o Specificity of indicator for the metal ion • Bi forms a highly stable complex and can be titrated
o Stability constant smaller than that on the at a pH as low as 1 or 2
metal – EDTA complex
Direct Titration Methods in Complexometry OXIDATION – REDUCTION METHODS
• Usual metal ions determined via direct titration with
EDTA include Ca2+, Mg2+, and Zn2+ • VILEORA and VDGEROA
OXIDATION REDUCTION
Preparation and Standardization of 0.05 M Na EDTA Valence Increase Decrease
• CaCO3 – primary standard Electrons Loss Gain
• 100.09 g/mol – MW Agent RA OA
• 0.050045 – mEq
Pharmaceutical Analysis 1 Midterms University of Negros Occidental - Recoletos
(Quantitative Pharmaceutical Chemistry)
• Formula for mEq of OA and RA • Malic acid is converted to an equivalent amt of
calcium salt, then converted to CaC2O4, with the
oxalate being liberated and oxidized with
permanganate
• Titer value: 6.704mg of malic acid
Assay of NaNO2
• Table of Oxidizing Agents and their mEq Factor • Since NaNO2 is deliquescent, weigh in a stoppered
Std. Solution Formula f x 1000 bottle
Potassium
KMnO4 5000 • NaNO2 is introduced beneath the surface:
permanganate • this is because nitrous acid (HNO2) is oxidized by
Potassium KMnO4 to HNO3, and if HNO2 is acidified by H2SO4,
K2Cr2O7 6000
dichromate HNO2 is easily volatilized therefore it must be
Potassium introduced beneath the KMnO4 to prevent loss.
ferricyanide • Allowing to stand for 5 min: ensures oxidation
Potassium completion
bromate KBrO3 6000
• Heating to 40 degrees Celsius: optimal temperature
Ceric sulfate Ce(SO4) 2 1000 for reaction completion
Iodine I2 2000
Bromine Br2 2000 CERIC SULFATE TITRATION (CERIMETRY)
Ferric alum FeNH4 (SO4)2 • Ce(SO4)2 in dil. H2SO4 is a strong OA
• Considerably more stable than KMnO4
• Table of Reducing Agents and their mEq Factor • Orthophenanthroline – indicator
Std. Solution Formula f x 1000 • From orthophenanthroline (colorless) to ferrous
Ferrous complex (red) to ferric complex (blue)
Fe(NH4)2(SO4)2
ammonium 1000 • Arsenic trioxide (As2O3) – primary standard
6H2O
sulfate • Osmium tetroxide – added as catalyst for the
Potassium reaction between Ce4+ and the arsenite ion (AsO2-)
KAsO2 2000
arsenite • Example of assay using cerimetry: Assay of FeSO4
Titanium tablets
TiCl3 1000
chloride
Sodium Assay of Ascorbic Acid
Na2S2O3 1000
thiosulfate • A solution of dichlorophenol – indophenol is
Arsenic standardized using ascorbic acid (RS), USP.
As2O3 4000
trioxide • Dichlorophenol – indophenol is used as a standard
Oxalic acid H2C2O4 2000 OA in the determination of ascorbic acid in ascorbic
acid tablets and injections.
PERMANGANATE METHODS (PERMANGANOMETRY) • No indicator is necessary
• KMnO4 is a self-indicator • Blue in alkali
• Endpoint is a distinct pink color • Red in acid
• Titration with KMnO4 should never be titrated from • Colorless in reduced form
Mohr burets • Titration is done in the presence of metaphosphoric
• Na2C2O4 is the best standard to use for KMnO4 acid and acetic acid with the standard solution, until
standardization a distinct rose pink color persisting for at least 5
• Sulfuric acid is added to prevent formation of MnO2 seconds
Assay of H2O2 IODIMETRIC AND IODOMETRIC METHODS
• Expressed in %w/v
• Should contain 2.5 – 3.5g/100mL (10 volumes) or 5.0 IODIMETRY IODOMETRY
– 7.0g/100mL (20 volumes) Analyte Reducing Agent Oxidizing Agent
• H2O2 is an oxidizing agent but acts as a reducing Method Direct Residual
agent in this assay VS 0.1N Iodine VS 0.1N Na2S2O3
Starch TS Starch TS
Assay of Cherry Juice for Malic Acid Indicator
Before titration Before EP
• Indirect method of MnO4- oxidation Endpoint Blue – black Colorless
Pharmaceutical Analysis 1 Midterms University of Negros Occidental - Recoletos
(Quantitative Pharmaceutical Chemistry)
• Titer: 8.806 mg
Preparation of Starch TS (indicator) • Strong RA, wherein titration with iodine oxidizes it to
• Should be freshly prepared – deteriorates rapidly dehydroascorbic acid and iodine is reduced to iodide
• In hot water, starch granules burst and form a ion.
colloidal dispersion:
o Beta amylose - aka soluble starch
o Alpha amylose - aka amylopectin, insoluble
starch
• Mercuric iodide (HgCl2) is used as a preservative for
Starch TS
Preparation of 0.1N Iodine Solution
• Primary Standard: Arsenic Trioxide
• Solubilizing Agent: Potassium Iodide
• Indicator: Starch TS
• Buffering Agent: NaHCO3
• Secondary Indicator: Methyl Orange (for neutralizing
the excess NaOH with HCl)
Preparation of 0.1N Sodium Thiosulfate
• Primary Standard: K2Cr2O7
• Oxidizes iodide ion in presence of acid to an
equivalent amt of iodine
• Prepared using CO2 – free water
• Uses Na2CO3 as preservative to prevent hydrolysis
• CHCl3 (trichloromethane, chloroform) is added to
prevent bacterial growth
Preparation of 0.1N Potassium Arsenite
• Primary Standard: Arsenic trioxide
• KOH – neutralizes arsenic trioxide and forms
potassium arsenite (KAsO2)
• KHCO3 – alkalinizes (to about pH =9) which is
necessary for accurate results and a rapid reaction
with iodine.
Liberation of Iodine from KI and Titration with Na2S2O3
• Used for substances that are OA which cannot be
determined via direct titration with a std solution of
an RA are assayed indirectly
• Examples:
o Assay of Selenium Sulfide
o Assay of NaOCl
o Assay of CuSO4
Assay of NaOCl
• USP Spec: 4-6% w/w
• Reagents: KI, HAc
• VS: 0.1N Na2S2O3
• Indicator: Starch TS
Assay of Ascorbic Acid
• USP Spec: 99 – 100.5%
• VS: 0.1N I2
• Indicator: Starch TS
