QUALITY CONTROL AND

QUALITY ASSURANCE

MS. SHARMAINE S. NARCISO, RPh

 QUALITY
 The combination of
attributes or characteristics
of a product which, when
compared to a standard,
serves as a basis for
measuring the uniformity of
the product and
determines its degree of
acceptability.
DIVISIONS OF ANALYTICAL CHEMISTRY
CLASSIFICATION OF ANALYSIS

I. Based on sample size

II. Based on the extent of determination
III.Based on nature of methods
IV.Based on materials used
I. BASED ON SAMPLE SIZE

Ultramicroanalysis < 1 mg

Microanalysis 1 mg – 10 mg

Semi-microanalysis 10 mg – 100 mg

Macroanalysis 100 mg – 1 g
II. BASED ON THE EXTENT OF DETERMINATION

 Proximate analysis
➢ Total amount of a class or a grouP of active plant principles in a given
sample.

 Ultimate analysis
➢ Amount of a Specific constituent or a Single chemical species present
in the sample.
III. BASED ON THE NATURE OF METHODS
MISCELLANEOUS /
CLASSICAL INSTRUMENTAL
SPECIAL
-More accurate
-Involves the crude
-Also known as general/ -Based on specific
drugs and other natural
chemical/ wet/ physical or chemical
products.
stoichiometric method properties of the
analyte.
Examples:
Example : Titrimetric Examples: Acid value,
Spectrometry,
analysis, Gravimetric Ash content, Water
Polarimetry,
analysis content
Chromatography
 IV. BASED ON MATERIALS USED
A.Chemical = Titrimetric method
B. Physical = Instruments and special
apparatuses
C.Biological = Use of microorganism and
animals and parts thereof
THEORIES ON ACIDS AND BASES
ACIDS BASE

ArrHenius H ion OH ion

BROnsTed- PROton
PROton Donor
Lowry Acceptor
Electron Electron
LEwis
Acceptor Donor
PRINCIPLES OF ANALYSIS
pH
 Refers to the measure of acidity or alkalinity
 Negative logarithm of the hydrogen ion activity
H2O  H+ + OH –
Kw = [H+ ] [OH – ] = 1.00 x 10 -14
 pH - Measure of the hydrogen ion concentration
➢ pH = - log [H+ ]
 For water at equilibrium, [H+ ] is 1.00 x10 -7

➢ pH = - log [H+ ] = 7
 FORMULAS:
 pH = -log [H+ ]
 [H ] = inv log (-pH)
+

 pOH = -log [OH – ]

 [OH ] = inv log [-pOH]

–

 pKw = pH + pOH
 FORMULAS:
 pH = 14 – pOH
 pka = - log ka

Compute for pH of weak acid

1. Determine pka
II. Compute for pH using:
pH = 1 [pka – log C]
--------------------
2
 BUFFERS
 Compounds that resist changes in pH upon the addition of limited
amounts of acids or bases.
 pH of a buffer system is given by Henderson – Hasselbach equation:
[salt]
 pH= pka + log ------ WEAK ACIDS
[acid]
[base]
 pH= pkw - pkb + log -------- WEAK BASE
[salt]
 SAMPLE PROBLEM
1. Calculate the pH of a solution which contains 4.6x10-3 mole of
Hac and 5.3x10-2 of Sodium acetate in a liter of solution pKa
of 10.6
ANS: 11.66
2. Calculate the pH of weak acid with concentration of 0.1M and
ka of 1 x 10 -5
ANS: 3
 BUFFER CAPACITY
Buffer pairs:
 weak acids + salts of weak acids
 weak bases + salts of weak bases
Van Slyke equation gives the relationship between buffer
capacity and buffer concentration:
ka [H3O+]
β = 2.3 C -------------------
(ka + [H3O+]) 2
C = sum of the molar concentrations of acid and salt)
 Accuracy – pertains to Agreement of an
experimental results with true value.

 Precision – is the measure of Reproducibility of

data within a series of results.
 ERROR TYPES
 Determinate errors - Can be detected, corrected
and manipulated
 Example: human errors, faulty procedure
 Indeterminate errors - Intangible or difficult to
detect
 Differences in the judgement and skill of the analyst.
 TYPES OF QUANTITATIVE ANALYSIS
A.Volumetric Analysis – analysis involving the measurement of volume
of a solution of known concentration required to react with the desired
constituent.

 Divisions of volumetric analysis:

– Neutralization
– Precipitation
– Complexometry
– REDOX
 TYPES OF QUANTITATIVE ANALYSIS
PHYSICO-
VOLUMETRIC GRAVIMETRIC
SPECIAL METHOD CHEMICAL
ANALYSIS ANALYSIS
METHODS
Analysis involving the Analysis involving the Analysis which require a Analysis based on some
measurement of accurate measurement distinct type of specific physical or
volume of a solution of of weight of substance technique such as chemical property or
known concentration being determined which analysis of crude drugs, properties of the
required to react with may be isolated in pure assay of fats and fixed substance being
the desired constituent. form or converted to oils, assay of volatile oils analyzed with the use of
-Divisions: another substance of and assay of alkaloids. instruments such as:
– Neutralization known composition by spectrophotometer,
– Precipitation making it react chromatographic units,
– Complexometry quantitatively with polarographer,
– REDOX another substance polarimeter, fluorimeter.
usually a precipitant.
 VOLUMETRIC ANALYSIS

 Is the determination of the volume of a solution of known concentration required

to react with a given amount of a substance to be analyzed
 Essentials of titrimetry
a. Analyte (Titrand) is the chemical substance being analyzed or the active
constituent; sample.
b. Standard solution (Titrant) is a solution in which the concentration is accurately
known
 END POINT
 Experimental approximate of the equivalence point which could be
observable.
 Is shown by the change of color of the solution.
1. Visual endpoint - use of indicators
2. Electrometric endpoint - amperometry, conductimetry and high
frequency titration
3. Equivalence point or stoichiometric point or theoretical
endpoint- is the theoretical point at which equivalent amounts of the
analyte and the titrant have reacted.
GRADE OF REAGENT IN ORDER OF INCREASING
STABILITY

Technical grade
USP/NF grade
Chemically Pure reagents
Analytical Reagent grade
Primary Standard grade
 TITER
 Strength in grams per milliliter solution or the weight of a
substance chemically equivalent to 1 ml of a standard solution.
mL x N = g/meq
or
g/mL = N x meq
“Each ml of 0.1 N HCl is equivalent to 3.705 mg of Ca(OH)2”
 INDICATORS
 Chemical substance, which changes color at or very near the endpoint.
 Referred to as TS or Test solutions
 Used to avoid errors during titration
 Mixed indicators are prepared if it will not give a sharp color change
 Always keep in glass- stoppered bottles, protected from light
 Use only 3 drops of indicators unless otherwise specified
 When weak acid is titrated with strong alkali, use phenolphthalein
 When weak alkali is titrated with strong acid, use methyl red
INDICATORS FOR NEUTRALIZATION
Color change
Indicator Acid Base
Malachite green Yellow Green
Methyl orange Pink Yellow
Methyl red Red Yellow
Bromothymol blue Yellow Blue
Phenolphthalein Colorless Pink or red
Thymol blue Yellow Blue
Bromocresol green Yellow Blue
Bromophenol Blue Yellow Blue
Phenol Red Yellow Red
 INDICATORS (OTHERS)

Precipitation Complexometry REDOX

•Dichlorofluorescein • Dithiazone • Iodine TS
•Eosin Y • Eriochrome black • Potassium
•Potassium • Hydroxynaphthol blue permanganate VS
chromate • Starch TS
•FAS
TITRATION VS STANDARDIZATION
TITRATION
 A PROCESS BY WHICH A VS IS BROUGHT INTO REACTION UNTIL
THE DESIRED REACTION IS ACCOMPLISHED.
 THE ACT OF ADDING AND MEASURING THE VOLUME OF TITRANT
USED IN THE ASSAY.

STANDARDIZATION
 THE PROCESS TO DETERMINE THE EXACT CONCENTRATION OF
SOLUTION.
 EXPRESSIONS OF CONCENTRATION

 A Normal Solution contains one gram equivalent weight of solute in a liter

of solution or one gram milliequivalent weight in a milliliter of solution.

N= g of solute or N = g of solute
g eq. Wt X Volume (L) mEq x vol (mL)
 A Molar Solution contains a mole (one gram molecular weight) in a liter of
solution or one millimole per milliliter of solution.
 A Mole is the molecular weight expressed in grams.
 A Millimole is one thousandth part of a mole.

M = no. of moles or M = g of solute

L of solution molar mass x L of sol.
 PRIMARY STANDARD
 Chemically pure solid substance almost 99.9% pure used in the standardization
of a solution.
 Other requirements are:
1. it must be easy to prepare and pure
2. it must be of definite known composition
3. it must be stable
4. it must react stoichiometrically with the substance present in the solution
5. it must be soluble in water and
6. it must have a fairly high equivalent weight
 PRIMARY STANDARD
FOR ACID Anhydrous pure Sodium carbonate
SOLUTIONS Calcium carbonate and
THAM
(trihydroxymethylaminomethane)
FOR BASIC Benzoic acid,
SOLUTIONS Potassium biphthalate and
Sulfamic acid.
 SECONDARY STANDARD

 Substance that is not necessarily pure but whose

exact purity is known.
 A standard solution is a commonly used as
secondary standard.
 WORKING FORMULA

 Using Primary Standard

no. of equivalents (titrant) = no. of equivalents (analyte)
ml x N = gm/ mEq

 Using Secondary Standard

mL x N = mL x N
 SAMPLE PROBLEM
1. 32 mL of sodium hydroxide solution was required
to titrate 30 mL of 1.025-N hydrochloric acid.
What is the normality of the sodium hydroxide
solution?
N1 V1 = N2 V2
( 32 mL) (N NaOH) = (30 mL) (1.025 N)
N NaOH = 0.9609 N
 SAMPLE PROBLEM
2. A sample of sodium carbonate (anhydrous) weighing 2.125 grams
required 40.2 mL of sulfuric acid for neutralization. Compute for the
normality of the acid solution.
N = Wt of primary std. (g)
mEq of primary std. X V
= 2.125g
0.053 g/meq X 40.2 mL
= 0.9974 N of sulfuric acid
 DIRECT TITRATION VS RESIDUAL TITRATION
DIRECT TITRATION
 ONE IN WHICH THE
ANALYTE IS TREATED WITH
TITRANT, AND THE VOLUME
OF TITRANT REQUIRED FOR
COMPLETE REACTION IS
MEASURED.
 % Assay = N x V x MEQ x 100
wt of sample
RESIDUAL TITRATION
 A MEASURED EXCESS OF THE STANDARD
SOLUTION IS ADDED TO THE SAMPLE TO
ACCOMPLISH A DESIRED REACTION AND
THE EXCESS IS THEN TITRATED WITH
ANOTHER STANDARD SOLUTION.
 KEYWORDS: “EXCESS…” “BACKTITRATED
WITH”
 % Assay = (mLxN)1 – (mLxN)2 x MEQ x 100
wt of sample
TYPES OF VOLUMETRIC ANALYSIS
NEUTRALIZATION PRECIPITATION COMPLEXATION REDUCTION-OXIDATION
REACTION METHOD METHOD METHOD
▪ Neutralization ▪ Analyte is titrated ▪ (complex- ▪ Chemical reaction in which
reactions are with a standard formation the oxidation states of a
chemical processes solution of a method) certain atoms change.
whereby an amount precipitating agent in ▪ Is the process ▪ Reactions in which
of an acid has reacted the presence of based on the electrons are transferred
with an equivalent suitable indicator formation of a between reactants.
amount of a base with ▪ Applies the complex
the production of salt solubility product substance in the
and water. principle course of
Divisions: ▪ Also called analysis. Divisions:
1. Acidimetry Argentometric 1. Permanganometry
2. Alkalimetry titration 2. Cerimetry
3. Iodimetry and Iodometry
 Aqueous Non-Aqueous
ACIDIMETRY ALKALIMETRY ACIDIMETRY ALKALIMETRY
Sodium
Volumetric Perchloric acid in
HCl, Methoxide in
solution NaOH Glacial acetic acid
Sulfuric acid ethyl alcohol or
/ Dioxane
toluene
Primary Potassium
Sodium bicarbonate KHP
standard biphthalate
Secondary
NaOH HCl
standard
Sodium hydroxide,
H3PO4, H3BO3,
Direct Sodium Bicarbonate, Methacholine Phenytoin
HCl
Sodium Salicylate
Zinc oxide, Milk of
Residual Magnesia, ASA
Methenamine
 PRECIPITATION METHOD
METHOD MANIFESTATION Primary Std VS INDICATOR EXAMPLE
VOLHARD Formation of insol. AgNO3 NH4SCN FAS / Ferric alum / Aminophylline,
(Residual) colored complex Fe (NH4)2 (SO4)2 Nacl

MOHR (Direct) Formation of ppt. NaCl AgNO3 Potassium SLS for NaCl
Chromate content

GAY – LUSSAC Cessation of ppt. NaCl AgNO3 No indicator NaCl

LIEBIG Appearance of turbidity KHP Na tetraphe-nyl BpB Organic nitrogen

boron cpds.
FAJANS Change in the color of NaCl AgNO3 Adsorption Phenylephrine
silver halide ppt. indicators: DCF, HCl,
Eosin Y TS,TEE TS Tubocurarine HCl,
Meperidine
 ENDPOINT
 Determined by:
A. Cessation of precipitation or
appearance of turbidity
B. Instrumental methods
C. Use of internal indicators
 COMPLEXATION METHOD
 Complexometry (complex-formation method) is the process
based on the formation of a complex substance in the course of
analysis.
 Uses: For analysis of Calcium, copper, mercury, magnesium, zinc,
aluminum and bismuth
 EDTA will react with metal ions to form a water-soluble stable
complex or a chelate compound.
METALS DETECTED BY INDICATORS
 TYPES OF COMPLEXOMETRIC TITRATIONS
A. Direct titration
 The simplest and most convenient titration
method used in complexometry
 Similar to acid base titrations
 Ex. Assay of Calcium Chloride
Limitations: slow complex reaction
 Analysis: Cu, Mn, Ca, Ba, Br, Zn, Cd,
Hg, Al, Sn, Pb, Fe, Mo, Co, Nic,V, Ga,
Cr, Bi
B. Residual Titration/ Back
 A standard EDTA solution is
added to the metal solution,
which is to be analyzed and the
excess is back titrated with
another standard solution.
 Ex. Determination of Manganese
(EDTA, Zinc VS, Eriochrome
black TS)
 MOLARITY
 no. of moles per liter of solution

g solute/ molar mass g solute

M= ---------------------- = -------------------
L of soln (molar mass) (L of soln)

M x Vol x Mol wt = grams

 ANALYSIS
1. What is the volume of NaOH solution with a concentration of 0.123N
needed to react with 0.2131g sulfamic acid (SO3NH3) sample ?
ANS: 17.86 ML
2. If 30ml of an acid solution reacts with the 32.1 ml 0.0121N NaOH,
a. what is the concentration of the solution?
b. what is the sodium carbonate titer of the acid solution?
ANS: A. 0.0129 N B. 0.68 MG
3. What volume of 0.05015-N thiocyanate solution would be required to
titrate the excess from 50 mL of 0.1-N AgNO3 that was added to a
solution of 0.2215 gram of NH4Cl (53.5) which is 99.5% pure?
Ans. 17.56 ml
4. A 200 mg pure CaCO3 was acidified and dissolved in 500 ml of
solution. A 50-ml sample required 25 ml of an EDTA solution for
titration. Find the M of the solution.
ANS: 0.008 M
 MASKING
 The term used to indicate the determination of a metal in the presence of another
metal.
 This may proceed by adjusting the pH or with the use of auxilliary complexing agents
like:
Masking Agents Masks:
Thioglycols Hg, Cu, Bi
Triethanolamine / TEA Fe, Al, Mn
Potassium Cyanide Zn, Co, Ni, Cu
Ammonium Fluoride Mg, Al Ca
Ascorbic acid, Tartrates,
Citrates
 OXIDATION-REDUCTION METHOD
▪ Chemical reaction in which the oxidation states of a certain
atoms change.
▪ Reactions in which electrons are transferred between
reactants.
▪ The simplest type of a REDOX reaction is the direct
combination of elements.
Ex.
 Mg + O2 MgO
 Zn + H₂SO₄  ZnSO₄ + H₂
 Oxidation Reduction
 Valence  Valence
 Increase  Decrease
 Loss  Gain
 Electron  Electron
 Oxidation  Reduction
 Reducing
 Oxidizing
 Agent
 Agent
 Gram-equivalent weight of an oxidizing and reducing agent may be
defined as the weight of the substance which involves in reaction,
the reducing or oxidizing equivalent of one gram-atom of hydrogen

formula weight of the substance

MEQ = --------------------------------
total change in the oxidation number
 STANDARD SOLUTIONS
▪ OXDIDIZING AGENTS – KMnO4, I2, Br, CeSO4, FAS,
Potassium Bromate, Potassium ferricyanide, Potassium
iodate

▪ REDUCING AGENTS – C2H2O4, FeSO4, Na2S2O3,

Potassium arsenite, Ferrous Ammonium Sulfate, Titanium
Chloride.
 METHOD PERMANGANOMETRY CERIMETRY IODIMETRY IODOMETRY

STANDARD KMnO4 C2H2O4 Ce(SO4)2 Ferrous I2 Na2S2O3 Na2S2O3

SOLUTION Ammoniu
m Sulfate

1º or 2º Na2C2O4 KMnO4 VS As2O3 Ce(SO4)2 As2O3 K2Cr2O7 K2Cr2O7

STANDARD VS
INDICATOR No indicator Orthophenanthroline Starch TS Starch TS
ENDPOINT LIGHT PINK W/ Reagent= RED BLUE COLOR DISAPPEARANCE OF
W/O Reagent= BLUE COLOR
GREE/BLUE
DIRECT Hydrogen Peroxide Ferrous sulfate Tablets Ascorbic acid, Copper Sulfate, Sodium
Potassium Antimony Hypochlorite
Tartrate (Tartar
Emetic)
INDIRECT Malic acid in Cherry Juice,
TiO2, MnO2

RESIDUAL Potassium Nitrite, Sodium KCl in Ringer’s Calomel, Antipyrine, Phenol, Resorcinol, PbO
Nitrite solution and injection. Sodium Bisulfite
IODIMETRY
ASSAY OF REDUCING AGENTS
INVOLVES DIRECT TITRATION
RXN W/ IODINE VS TITRATION OF EXCESS
W/ POTASSIUM ARSENITE OR SODIUM
THIOSULFATE VS
INDICATOR: STARCH TS
ENDPOINT: BLUE COLOR
EXAMPLES: ASCORBIC ACID, TARTAR
EMETIC, POVIDONE IODINE
IODOMETRY
ASSAY OF OXIDIZING AGENTS
INVOLVES INDIRECT TITRATION;
LIBERATION OF I2 FROM KI
TITRATION WITH POTASSIUM ARSENITE
OR SODIUM THIOSULFATE VS
INDICATOR: STARCH TS
ENDPOINT: DISAPPEARANCE OF BLUE
COLOR
EXAMPLES: SELENIUM SULFIDE, SODIUM
HYPOCHLORITE, CUPRIC SULFATE
5. 1. A 1.100-g sx of sodium nitrite was dissolved in sufficient
water to make 100 ml. A 10-ml sx of the soln was added to
50.0 ml in 0.1 N potassium permanganate in the presence of
sulfuric acid. The mixture was treated with 25.0 ml of 0.0975N
oxalic acid and titrated with 4.58 ml of 0.1N potassium
permanganate. Calculate the percent NaNO2 in the sample.
NaNO2 + KMnO4 + H2SO4  HNO3 + MnSO4
+ K2SO4 + Na2SO4 + H2O
6. A 04.0050 g sample of chlorinated lime was mixed with enough water
to make 1L. A 100-ml sample of the mixture was treated with KI and
acetic acid and titrated with 22.61 ml of sodium thiosulfate solution. A
20-ml of sample of the thiosulfate solution was found to be equivalent
to 0.3689 g of pure iodine. Compute for the chlorine content of the
chlorinated lime.
Cl  KCl

Ans. 29.14%
 GRAVIMETRIC ASSAY
 Gravimetric analysis consists of isolating from the sample the constituent to
be determined in its pure state and weighing it accurately
 Chemical Factor = Defined as the weight of the constituent determined or
sought and is equivalent to the unit weight of a given substance.
 EX: The chemical factor of sodium sulfate in barium sulfate is
Na2SO4 142.52
----------- = --------- = 0.6086  C.F.
BaSO4 233.43
 W x CF x 100
% = ------------
wt of sx

 % Na2SO4 = wt of BaSO4 x CF x 100

---------------------
weight of sample
 SAMPLE PROBLEMS

A 0.3056-g sample of soluble chloride was analyzed gravimetrically for Cl

and 0.7265 g of AgCl was obtained. Calculate the Cl and NaCl contents of
the sample, expressing each in %w/w
Cl (35.5) NaCl(58.5)
CF of Cl = --------- CF of NaCl =----------
AgCl (143.5) AgCl(143.5)

Weight of AgCl x CF
% purity = ----------------- x100
wt of the sx
SAMPLE PROBLEM
1. An unknown sample of a soluble sulfate weighing 1.80 g yielded 0.90 g of
BaSO4. Compute for % S in the sample.
C.F. = S (32)
BaSO4 (233.43)
C.F. = 0.1371
% S = WEIGHT OF PPT X CF X 100
WEIGHT OF SAMPLE
= 0.90 G X 0.1371 X 100
1.80 G
= 6.855%
 DETERMINATION OF ASH

 The ash content of a crude drug is the residue left

after incineration.
 It usually represents the inorganic salts naturally
occurring in the drug adhering to it.
 It may also include inorganic matter added for the
purpose of adulteration.
APPROXIMATE TEMPERATURE EQUIVALENTS

Very dull-red heat = 500 to 550 C

Dull red heat = 550C to 700C.
Bright red heat = 800C to 1000C
will convert carbonates to
oxides and alkali chlorides
if present may lose some
chlorides by volatilization.
Yellow red-red heat = 1000 to 1200C
White heat = 1200 to 1600C
ASH DETERMINATION

 Total ash
% total ash = wt. of ash x 100
wt. of sx
 Acid-insoluble ash
% acid insoluble ash = wt of acid insoluble ash x 100
wt of sample
From the following data, compute for % total ash and % acid
insoluble ash. Does the sample conform with the official requirement

A. wt of empty crucible ………………………. 52.452 g

B. wt of crucible and sample …………………..61.684 g
C. wt of crucible and sample after drying …60.320 g
D. wt of crucible and residue left after incineration …..53.005 g
E. wt of crucible and acid – insoluble residue ……. 52.4858 g

Official requirement : ash limit – 6%, acid-insoluble residue limit – 0.5%

 MOISTURE DETERMINATION

 Official Drugs vary in their water content. Water available

either as water of crystallization (hydrates) or as water in the
adsorbed form.
 Determination of this constant is necessary to specify certain
water content limits in the drug monographs.
 In order to ensure uniformity in the official drugs
WATER CONTENT IS DETERMINED BY ANY ONE OF THE SIX
METHODS:

1. Gravimetric Method – for drugs containing no constituents other than water, volatile
at 105C.
2. Gravimetric Method – for drugs containing ether-soluble constituents, volatile at
105C.
3. Azeotropic Method or toluene distillation - for the determination of moisture
content of many vegetable drugs containing 2% or more of moisture
4. Titrimetric Method or Karl Fischer Method - for crystalline compounds that contain
water of hydration or absorbed water
5. Dew Point Method – for determining Water at Very Low Concentration
6. Electrolytic Hygrometric – for determining Extremely Low Concentration of Water
METHOD I - KARL FISCHER METHOD

Anhydrous Prevents the

pyridine-sulfur
methanol complex
HYDROIODIC ACID
Iodine React with water
Sulfur dioxide
SULFUR TRIOXIDE

Prevents reverse
Pyridine reaction
PRACTICE PROBLEMS:
1. Moisture content of citric acid was determined by the Karl-
fischer Method and the following data were obtained
wt of citric acid …………………………4.8 g
vol of reagent used ……………………20 ml

water equivalence factor of the reagent was determined by

titrating 0.350g of sodium tartrate with 10 ml of KFR,
determine the water content of citric acid
METHOD II – AZEOTROPIC METHOD
 The Azeotropic Method is specified for the determination of moisture content
of many vegetable drugs containing 2% or more of moisture.
 Its disadvantage is the need for a large amount if drug, from fifty (50) to one
hundred (100) grams must be used in order to secure a volume of water that
can be measured conveniently without considerable error.
METHOD III – GRAVIMETRIC METHOD
 When the drug contains matter other than water which is volatile at 105C,
the volatile ether soluble extractive must be determined and the weight of this
extractive is subtracted from the weight less by the drug upon drying, the
difference is the moisture content of the drug.
PRACTICE PROBLEMS

Weight of the powdered digitalis leaves ……………. 48.645

g
vol. of water collected water from the distillate…. 2.5 ml
USP, water limits is 2%

1. compute for the percent of moisture present in the sample

2. if exactly 50 g of digitalis was weighed, what would be the volume of water
collected if the percentage is 6%
 ACID VALUE
Acid Value- # of mg of KOH req’d to neutralize the FA in 1g of sx
-# of ml of 0.1 NaOH req’d to neutralize the FA in 1g of sx
-AKA: Acid number or Acidity index
 Acid value = VNaOH x NNaOH x 56.11 (MW
KOH/1000)
weight of the sample

 AV = mL of 0.1 NaOH
-------------------------- X 2
wt of Sample
PRACTICE PROBLEM
• Find the acid number of a rosin
sample weighing 1.100g which
required 28.00 mL of 0.1100 N
NaOH to bring about the
endpoint.
Acid value = VNaOH x NNaOH x 56.11
weight of the sample
 SAPONIFICATION VALUE

 also known as the SAPONIFICATION NUMBER OR

KOETTSDORFER NUMBER
 # of mg KOH required to neutralized FA and saponify esters
in 1G of subs
SV = AV + EV
𝑁 ( 𝑉𝑏𝑙𝑎𝑛𝑘 −𝑉𝑎𝑐𝑡𝑢𝑎𝑙 )(𝑁)(56.11)
SV = 𝑤𝑡.
 SAPONIFICATION
SUBSTANCE
VALUE

Carnuba wax 80-95

Castor oil 176-182

Cocoa Butter 188-195

Corn oil 187-193

Cotton Seed oil 190-198

Olive oil 190-195

Sesame oil 188-195

PRACTICE PROBLEM
Find the saponification value of cottonseed oil if a
1.532g of sample, refluxed with 25 ml of about 0.5
N alcoholic KOH, required 15.70 mL of 0.5100N
HCl for the residual titration. The blank was run
using the same volume 0f 0.5 N alcoholic KOH and
required 26.00 mL of 0.5100 N HCl to bring about
the endpoint.

( mL of HCl BT - mL of HCl AT) N x 56.11

S V= --------------------------------------------------------------
WT OF SX
 ESTER VALUE
 also known as ESTER NUMBER

 # of mg. needed to saponify the esters in 1g. of subs

- same formula as acid value
- if there is no FA , EV = SV
EV= SV-AV
 % Ester content = (Vb – Vsx) x N x meq. Wt. x 100
Weight of sample
 PRACTICE PROBLEM

If a sample of white wax is found to have an ester

value of 65.7 and a saponification value of 74.2,
what is the acid value of the sample?
 IODINE VALUE
 Also IODINE NUMBER
 Defined as the number of grams of iodine absorbed under specified condition by 100 grams of oil,
fat, wax or other substance.
 Measure degree of UNSATURATION

𝑁 𝑉𝑏 −𝑉𝑎 𝑥 0.1269
I𝑜𝑑𝑖𝑛𝑒 𝑣𝑎𝑙𝑢𝑒 = x100
𝑤𝑡.
Methods:
Method I: Hanus Method (use of Iodobromide)
Method II: Wij’s method
Method III: Hubl’s method <unofficial>
 TYPES OF FIXED OILS

TYPE IV EXAMPLES
DRYING >120 LINSEED OIL,
FISH OIL,
COD LIVER OIL
SEMI-DRYING 100-120 COTTONSEED
OIL,
SESAME OIL
NON-DRYING <100 OLIVE OIL,
ALMOND OIL
PRACTICE PROBLEM

1.) Determine the iodine value of an unknown

sample of oil weighing 0.21g if 26 mL and 12 mL
of 0.1100N of sodium thiosulfate are required for
the blank and residual titration respectively

IV= (26mL-12mL)x0.1100Nx0.1269 x100

0.21g
 ALDEHYDE CONTENT

% ALDEHYDE =
(mL ACTUAL – mL BLANK) x N x meq X 100
wt of Sample
 PHENOL CONTENT

ML OF EUGENOL = ML OF SAMPLE – ML OF
RESIDUAL LAYER
% PHENOL = ML OF EUGENOL X 100
ML OF SAMPLE
 DISSOLUTION
 Computing for Q value or % dissolved

abs. sx conc. std.

------------- = ---------------
abs. std. conc. sx.

Abs sx ave wt of sx
% Dissolved (Q) = ---------- x Conc Std x DF x ----------------- x 100
Abs std wt of ind sx
-----------------------------------------------------
Label Claim
vol of medium x vol for dilution
DF= -----------------------------------------------------
vol of sample
 ASCORBIC ACID 500 MG
The test used 4 paddle type apparatus set at the following parameters:
Medium - water, 900 mL
Speed - 50 rpm
Time - 45 minutes
Dilution - withdraw 1 ml of sample and dilute to 70-ml VF
RS - weigh 200 mg of Ascorbic acid (RM) dissolve in 1000 mL, withdraw 50 mL of the RS transfer
in 250 mL VF and fill to volume
Absorbance Conc. Of std. Weight of sample
Std 0.567
Sx 1 0.548 511 mg
Sx 2 0.557 498 mg
Sx 3 0.565 503 mg
Sx 4 0.562 493 mg
Average wt of 4 tablets:__________
a. compute for Q values of samples 1 to 4
b. give the disposition

NOTE: Dilution factor for dissolution is computed as:

vol of medium x vol for dilution
DF= --------------------
vol of sample
 DF = (900 ml x 70 ml) / 1ml = 63,000 ml
 Conc of std. = 0.04 mg/ml
 Ave wt = 501.25 mg
 Q1 = 477.82 mg
 Q2 =
 Q3 =
 Q4 =
 CHROMATOGRAPHY
Sample Problem:
Carbocistein 500mg Capsule
Weight of RS: Weigh 60.9 mg dilute to 100 mL, take 5mL dilute to 100mL
Weight of Sample: Weigh 59.8 mg dilute to 100 mL, take 5 mL dilute to 100mL.
Total Weight of 10 Carbocistein capsules = 6015mg
Weight of empty capsule = 98 mg
Peak Area of Standard = 90491 nm2
Peak Area of Sample = 85414 nm2
Specifications: NLT 95% NMT 115%
1. DETERMINE THE CONCENTRATION OF ACTIVE
CONSTITUENT IN THE FINAL DILUTION

Concentration of Sample (Actual)

Peak Area of Sample
= ------------------------------- X Conc. of Standard
Peak Area of Standard
Answer:
85414 nm2
= ------------------------------- X 30.45 mcg/ml
90491 nm2

88

= 28.74 mcg/ml
2. DETERMINE THE CONCENTRATION OF THE SAMPLE TAKEN
IN THE FINAL DILUTION.

Concentration of Sample (Theoretical)

Answer:
Concentration of Sample in the Final Dilution
59.8mg 5ml 1000ug
= ---------- x ------ x -------
100ml 100ml 1mg

89

= 29.9mcg/ml
3. DETERMINE THE QUANTITY OF RIFAMPICIN PRESENT PER
CAPSULE.

Amount (mg/dosage form)

Conc. of Sample (Actual) X Average weight
= ---------------------------------------------------------------
Conc. of Sample (Theoretical)
Answer:
28.74mcg/ml x 503.5 mg
= --------------------------------
29.9mcg/ml 90

= 483.97 mg
4. DETERMINE THE PERCENT LABELLED AMOUNT.

% Potency (% Assay)
Amount present per dosage form
= --------------------------------------------- X 100
Label Claim
Answer:
483.97mg
= ------------- x 100 = 96.794%
500.00mg 91
5. DETERMINE THE PERCENT PURITY OF THE SAMPLE.

% Purity
Conc. of Sample (Actual)
= --------------------------------------- x 100
Conc. of Sample (Theoretical)
Answer:
28.74 mcg/ml
= ------------------ x 100 = 96.12%
92
29.9 mcg/ml