This document provides an overview of pharmaceutical analysis techniques. It discusses qualitative and quantitative analysis, various analytical methods including chemical, physical and biological methods. It describes different techniques for expressing concentration such as molarity, normality, percent solutions. It also discusses primary and secondary standards used for standardization of analytical methods and preparation of common standard solutions like hydrochloric acid, sodium hydroxide and sodium thiosulfate. The document aims to introduce fundamental concepts of pharmaceutical analysis.

1. Unit - 1
Presented by;-
Mr perfect

2. chapters
(1) pharmaceutical analysis - defination and scope.
(2) errors
(3) pharmacopoeia

3. CHAPTER - 1
PHARMACEUTICAL ANALYSIS
Defination And Scope

4. we read following topics:-
(1) Different techniques of analysis.
(2) Methords of expressing concentration.
(3) primary and secondary standards.
(4) prepration and standardization of varioys molar and
normal solutions.
(oalic acid ,sodium hydroxide, hydrochloric acid, sodium
thiosulphate, sulphuric acid, potassiium permagnate, and ceric
ammonium sulphate. )

5. what is Analytical chemistary
• Application of a process or series of processes in
order to indentify and quantify the substance, the
components of a solution or mixture, or the
determination of the structure of chemical
compounds.

6. Part - 1

7. (1)

8. Types of analyte on basis of size
1. Macro Analysis - 0.1g
2. Meso (Semimicro) Analysis - 0.01 to 0.1g
3. Micro Analysis - 0.001g to 0.01g
4. Submicro Analysis - 0.0001g to 0.001g
5. Ultromicro Analysis - 0.0001g

9. Different techniques of analysis
analysis is broadly divided into two categories.
(1) qualitative analysis.
(2) Quantative Analysis.

10. {1} Qualitative Analysis
It gives information about atomic and molecular
species or the functional group in sample.
Mp,bp,specific gravity, RI,Absorbance, Optical
rotation, Viscosity, particle size,etc

11. {2} Quantitative Analysis
It gives relative amount of one or more of the
analyte in numerical terms.
it measure the concentration or amount of each
substance in a sample.

12. Analytical Methods
(1) Chemical Methods
(2) Physico-chemical Methods
(3) Microbiological Methods
(4) Biological Methods
we are going to discuss these in detail now.

13. 1. Chemical Methods

14. (A1) volumetric analysis

15. • (A) neutralization acid - base titration;-
it involves neutralization acid base reaction in
presence of water as a solvent.
• (B) non - aqueous acid base titration:-
it involve reaction in between acid and base in
presence of non aqueous solvent.
i.e = organic solvent.

16. • (C) precipitation titration:-
it is a precipitation formation reaction. in this
titration the reacting substance reacts with
standard solution to form a precipitate or
slightly soluble salts.

17. (D) oxidation - reduction titration {redox} :-
in this titration stimulataneous oxidation - reduction
reaction occur.
it include the methords where one reacting substance is
oxydised while other one get reduced.

18. (E) complexometric titration:-
it is a complex formation reaction.
in this titration the reacting substance react with standard
solution to form a solute but very slightly dissociated
coplex.

19. (A2)Galvanometric analysis

20. galvenometric analysis
it is quantative determination of an analyte based on the
mass of a solid by the process of isolating definate
compound of element in pure form .
in this technique substance under determination is
converted into insoluble precipitate which is collected and
weighed.

22. Present day Analysis Instruments
Better and Faster
 More Data (Images)
Miniaturization
Better data processing methods - Chemometrics

23. Importance of Pharmaceutical Analysis
 Identification of raw materials (in-process and finished
product).
 Determination of additional impurities.
 Stability of the drug.
 Strength and concentration of the chemical compound.
 Determine molecular weight of the chemical compound.
 Structure elucidation of synthetic compound.

24. Concentrations of drug in plasma or
biologicalfluids.
 Determine pka values, partition coefficients ,
solubilities,andstability of drug under
development.

25. MCQ
• Which one of the following is Quantitative Analytical
Method?
(1) Viscosity determination (2) pH measurement
(3) Refractive index (4) Titrations
Correct Answer:- Titrations

26. 2
• All of the following are electrochemical methods of
analysis except.
(1) Conductometry (2) Potentiometry
(3)Amperometry (4) Refractometry
Correct Answer : - Refractometry

27. 3
• Quantitative determination principle in titrimetric methods
are based…
(1) On the basis of measurement of Volume
(2) On the basis of absorbance of sample
(3) On the basis of pharmacological response
(4) On the basis of measurement of conductance
correct answer :- On the basis of measurement of Volume

28. Part - 2

29. • (2)
methords of expressing
concentration

31.  In all the techniques of quantitative analysis the
use of solutions requires some basis for the
expression of solution concentration.
(1) Normality
(2) Molarity
(3) Molality
(4) Percent Solution
(5) Formal Concentration
(6) Parts per Million (PPM)

32. (1) Normality
Number of gram equivalent of solute (Substance)
dissolved in one litre (1000 ml) of solution is known as
Normality.
 Normality is indicated by N.

33. (2) Molarity
Number of moles of solute
(Substance) dissolved in
one litre (1000 mL) of
Solution is called as
Molarity.
1 gm in 1000 ml = 1 mol.
Molarity is indicated by M.

34. (3) Molality-
A molal solution contains 1 mole of solute per one
kilogram of solution ( 1 lit. of solvent) is called as Molality.
Molality is indicated by M.

35. (4) Percent (%) Solution
Sometimes the concentration is expressed in terms of per
cent (parts per hundred) also.
Percent Composition of a solution can be expressed as:
1. Per cent W/W = Weight of solute/ Weight of solution X
100
2. Per cent V/V = Volume of solute/ Volume of solution X
100
3. Per cent W/V= Weight of solute/ Volume of solution X
100

36. examples
• 1 %= 1gm of KCl ----------- in 100 ml of water
• 10 % = 10 gm of KCl ----------- in 100 ml of water
• 100 % = 100 gm of KCl ----------- in 100 ml of water

37. (5) Formal Concentration
• The concentration unit, formal, is similar to the more
familiar molar concentration in that it is calculated as the
number of moles of a substance in a liter of solution
Formal concentrations are notated or represented with the
symbol F.
The formal Concentration (Formality) is applicable to the
ionic substances.

38. (6) Parts Per Million
• Parts per million is frequently employed to express the
concentration of very dilute solutions and is express as
PPM
• Conc. In PPM = Mass of solute / mass of solution X 10
PPM

39. Part - 3

41. Standards
• In Pharmaceutical Analysis, the word standard means a
material containing a substance of our interest with a
known concentration. We can express this with definite
numbers with proper units.

42. Functions
To provide a reference using which we can determine
unknown concentration of solution
To standardization of volumetric solutions
Preparation of secondary standard
 To calibrate an instrument

43. types:-
standards are of two types:-
(A) Primary Standard.
(B) Secondary standard

44. (A) Primary Standards
• Primary standard is a reagent which is very pure,
generally representative of the number of moles the
substance contains and easily weighed.
• A Primary standard is a reagent that’s stable, it’s not a
hydrate /has no water of hydration, and has a high
molecular weight.
• Primary standards are typically used in titration to
determine an unknown concentration and in other
analytical techniques.

45. High level of purity, low reactivity (high stability), high
equivalent weight (to reduce error from mass
measurements )
 Not hygroscopic (to reduce changes in mass in humid
versus dry environments), non-toxic, inexpensive and
readily available
It should have a high relative molecular weight so that
weighing errors may be negligible.

46. The substance should be readily soluble under the
conditions in which it is employed.

47. The substance commonly employed as primary
standards are mention below…
Acid- base reactions: sodium carbonate Na2CO3, sodium
tetraborate Na2B4O7, potassium hydrogenphthalate
KH(C8H4O4), potassium hydrogeniodate KH(IO3)2.

48. Complex formation reactions: pure metals ( zinc, copper,
magnesium and manganese) and salts, depending upon
the reaction used.
 Precipitation reactions: silver, silver nitrate, sodium
chloride,potassium chloride and potassium bromide.
Oxidation- reduction reaction: potassium dichromate
(K2Cr2O7), potassium bromate (KBr), potassium iodate (
KIO3), sodium oxalate Na2C2O4 and pure iron.

49. (B) Secondary standard
Secondary standard is a chemical that has been
standardized against a primary standard for use in a
specific analysis. Secondary standards are commonly
used to calibrate analytical methods.
 A secondary standard is a substance which may be used
for standardization.
A secondary standard is a standard that is prepared in the
laboratory for a specific analysis. It is usually standardized
against a primary standard.

50.  It follows that a secondary standard solution is a
solution in which the concentration of dissolved
solute has not been determined from the weight of
the compound dissolved but by reaction (titration)
of a volume of the solution against a measured
volume of a primary standard solution

51. A secondary standard is a chemical or reagent
which has certain properties such as….
It has less purity than primary standard
 Less stable and more reactive than primary standard But
its solution remains stable for a long time
 Titrated against primary standard

52. Part - 4

53. (4)
(4)
Prepration and
standardization of varioys
molar and normal solutions.

54. Standard sollution
sollution of accuracy is known as a standard sollution.
it contain a known weight of reagent in a definate volume
of sollution.
it is nither possible nor it is essential to prepare
volumetric solutions of desired theoritical molarity.
A sollution of approximately desiered molarity is prepared
and standardised by titration against a sollution of a
prmary standard.

55. molecular formula :- H2C2O4 .2H2O = 126
Molecular weight :- 90.03
prepration :- Dissolve 6.3 gram of oxialic acid in sufficant
water to produce1000 ml.
Standardization:- pipette 25ml of the 0.1 NaOH and transfer it
into a clean conical falsk,to it add 2-3 drops of phenolphathalin
idicator and titrate with the sodium 0.1N oxalic acid solution until
colour changes from purpole to colourless.

56. reaction :-
H2C2O4(aq)+ 2NaOH(AQ) → Na2C2O4(Aq) + 2H2O(l)
factor calculation :-
1 mole of oxalic acid ≈2 mple of sodium hydroxide
1000ml of 1M H2C2O4≈ 80 gm of NaOH
1000 ml of 1M H2C2O4 ≈ 40gm of NaOH
1 ml of 0.1M H2C2O2.2H2O ≈0.0040g of NaOH

57. Sodium Hydroxide (1M)
• Molecular Formula : NaOH
• Molicular Weight : 40
• Prepration;-
Dissolve 40g of sodium hydroxide in sufficient carbon
dioxide free water to produce 1000ml. prepared sollution
store in bottles with well fitted suitable stoppers which
prevent access to atmospheric carbondioxide.

58. • Standardization :-
 when accurately about 5g of potassium hydrogen
phthalate, previously powerded and dried at 1200 for 2
hours and dissolve in 75ml of carbodioxode free water.
add 0.1 ml of phenolphthalein solution and titrate with the
sodium hydroxide solution until a permanent pink colour is
produced. Volumetric solution of sodium hydroxide must
be rstandarise frequently.

59.  reaction
• potassium hydrogen pthalate
+ → Sodium potassium
sodium hydroxide Phthalate
(NaOH) +
( H2O)

60.  Factor calculation
1 mole of NaOH ≈ 1 mole of potassium pthalate
1000 ml of 1M NaOH ≈ 204.2g of C8H5KO4
1ml of 1M NaOH ≈ 0.2042g of C8H5KO4

61.  Hydrocloric Acid (1M)
• Moleculae Formula :- HCL
• Molecular Weight :- 36.5
• Prepration:- dilute 85ml of hydrocloric acid with water to
produce 1000ml.
• Standardization :- weigh accurately about 1.5g of anhydrous
sodium carbonate, previously heated at about 2700c for 1 hour.
dissolve it in 100ml of water and add 0.1 ml of methyl red
sollution. add the hydrocloric acid slowly from a burette, with
constant stering, until the sollution become faaintlypink.

62. • heat the sollution to boil, cool and continue the titration .heat
again to boil and titrate further as necessary until the faint pink
colour is no longer affected by continue boiling.
reaction:- Na2CO3 + 2HCl → 2NaCl + H2CO3
H2CO3 → H2O + CO2↑
Factor calculation:-
2 moles of HCl ≈ 1 mole of anhydrous sodium carbonate.
2000 ml of 1M HCl ≈ 105.99g of Na2CO3
1 ml of 1M HCl ≈ 0.05299g of Na2CO3

63.  Sodium thiosulphate (0.1M)
• Molecular formula :- Na2S2O3
• Molecular Weight :- 158.11
• Prepration :- Dissolve 25g of sodium thiosulphate and 0.2g of
sodium carbonate in carbondioxide free water and dilute to
1000ml to 1000ml with the same solvent.
• Standardization:- dissolve 0.2g of potassium bromate, weigh
accurately, in sufficient water to produce 250ml. to 50ml of this
sollution, add titrate with the sodium thio sulphate solution using
starch sollution, added towards the end of titration, as an indicator
until the blue colour is discharged [ I2 forms blue coloured
complex with starch]. re standarise the sollution frequently.

64. Reaction :- KBrO3 + HI → HIO3 + KBr
IO3
‾ + 5I‾ + 6H+ → 3I2 + 3H2O
3[2Na2S2O3 + I2 → Na2S4O6 + 2NaI]
factor calculation:- 6Na2S2O3 ≈ 3I2 ≈HIO3 ≈ KBrO3
6 moles of Na2S2O3 ≈ 1 mole of KBrO3
6000ml of 1M Na2S2O3 ≈ 167g of KBrO3
1 mole of 0.1M Na2S2O3 ≈ 0.002783g of KBrO3

65.  Sulphuric Acid (0.5M)
Molecular Formula :-H2SO4
Molicular Weight - 98.08
Prepration:- Add slowly, with stirring, 27ml of sulphuric acod to
about 1000ml of water, allow to cool 250c.
Standardization;- weigh accurately about 1.5g of anhydrous
sodium carbonate, previously heated at about 2700 for 1 hour.
Dissolve it in 100ml of water and add 0.1ml of methyl red solution
becomes fainty pink. heat the sollution to boil, cool and continue
then titration. heat again to boil and titrate further as necessary
until the faint pink colour is longer affected by continued boiling.

66. reaction:- Na2CO3 + H2SO4 →Na2SO4 + H2CO3
H2CO3 → H2O + CO2 ↑
Factor calculation :-
2 moles of H2SO4 ≈ 1 mole of anhydrous sodium carbonate
1000 ml of 1M H2SO4 ≈ 105.99 of Na2CO3
1 ml of 0.5M H2SO4 ≈ 0.05299g of Na2CO3

67. chapter 1 complete’s here
now we are going to start second
chapter.

68. CHAPTER - 2
ERROR’S

69. What is Error…?
• Error is the difference between the true result (or
accepted true result) and the measured result.
• If the error in an analysis is large, serious consequences
may occur.

70. • As reliability, reproducibility and accuracy are the
basis of analytical chemistry.
• A patient may undergo expensive & even
dangerous medical treatment based on an incorrect
laboratory result because of an analytical error.

71. Error = measured mean value – true value
• The difference between the experimental value
and true value is termed as Absolute error.
• Absolute error may be negative or positive.

72. Types of errors :-
There are two principle types of error in analysis :
(A) Determinate or systematic error
(B) Indeterminate or random error

73. Determinate Errors:-
They are caused by faults in the analytical procedure or
the instruments used in the analysis.
Determinate errors are systemic errors i.e. they are not
random.
As the name indicates that the cause of this type of error
may be found out & then either avoided or corrected.

74. A particular determinate error may cause the
analytical results produced by the method to be
always too high.
Another determinate error may render all results
too low.Sometimes the error remains constant;
All results are too high or too low by the same
amount.

75. Determinate error can be additive or they can be
multiplicative . It depends on the error & how it
enters into the calculation of the final result.
This determinate error could be the result of an
incorrectly calibrated balance.

76. If the balance is set so that the zero point is
actually 0.5 mg high, all masses determined
with this balance will be 0.5mg too high.
If this balance was used to weigh any std. sol.
Used in the laboratory, the std. concentration will
be erroneously high,and all of the results
obtained using this std. will be erroneously high.

77. If the balance is set so that the zero point is
actually 0.5 mg high, all masses
determined with this balance will be 0.5mg
too high.
If this balance was used to weigh any std.
sol. Used in the laboratory, the std.
concentration will be erroneously high,and
all of the results obtained using this std. will

78. Measured mean value – True value = Absolute value
Absolute value is the difference between the
true and measured value.

79. Determinate errors may arise from some faulty step in
the analytical process.
The faulty step is repeated every time the determination
is performed. Whether a sample is analyzed 5 times or
50 times, the results may agree with each other but differ
widely from the true answer.
• Systemic error is under the control of the analyst.

80. How are determinate errors identified and
corrected...?
• One is to analyze the sample by a completely different
analytical procedure that is known to involve no
systematic errors. Such methods are often called
“standard methods”; they have been evaluated
extensively by many laboratories & shown to be precise
and accurate.

81. If the results from two analytical methods agree, it is
reasonable to assume that both analytical procedures are
free of determinate errors.
The 2nd method is to run several analyses of a
reference material of known, accepted concentration of
analyte. The difference between the known concentration
and that measured by analysis should reveal the error.

82. If the results of analysis of a known reference std. are
consistently high or low, then a determinate error is
involved in the method.
Determinate error can arise from uncalibrated balances,
improperly calibrated volumetric flasks or pipettes,
malfunctioning instruments, impure chemicals, incorrect
analytical procedures or techniques and analyst error.

83. Analyst error :-
They may be the result of inexperience, insufficient training.
An analyst may use the instrument incorrectly,Perhaps by
placing the sample in the instrument incorrectly each
time.
Setting the instrument to the wrong conditions for
analysis. Misreading a meniscus in a volumetric flask as
high or low.

84. Operational and Personal errors :-
• These are depends on factors for which the individual
analyst is responsible and are not connected with the
method or procedure they form part of the personal
equation of an observer.
• Mechanical loss of materials in various steps of analysis.
• Underwashing or over washing of precipitates.
• Ignition of ppts at incorrect temperatures.

85. Some analyst are unable to judge color changes sharply
in visual titrations, which may result in slight overstepping
of the end point.
Some other analyst – related errors are :
Carelessness
i.e. copying the wrong information
into a lab notebook or onto a label.

86. steps by which we can reduce the errors..
Proper training, experience, and attention to detail can
correct these errors.
Reagents and instrumentation :
Contaminated or decomposed reagents can cause
determinate errors.
Prepared reagents may also be improperly labeled.

87. Impurities in the reagents may interfere with the
determination of the analyte, especially at the ppm level
or below.
Numerous errors involving instrumentation are possible,
including.
Faulty construction of balances,
Incorrect instrument alignment,
Incorrect wavelength settings,
Use of uncalibrated or improperly calibrated weights.

88. These problems can be eliminated by a systematic
procedure to check the instrument settings and
operation before use. Such procedures are called
in the m any labs.
There should be a written SOP for each instrument and
each analytical method used in the laboratory.

89. In instrumental analysis, electrical line voltage fluctuations
are a particular problem. This is especially true for
automated instruments running unattended overnight.
Instruments are often calibrated during the day, when
electrical power is in high demand.
At night ,when power demand is lower, completely
changing the relationship between conc. Of analyte and
measured signal.

90. Analytical Method :
The most serious errors are those in this methord itself.
Examples of method include :-
Incorrect sampling
Incomplete reaction for chemical methods,
Unexpected interferences from the sample itself or
reagents used.
Loss of analyte during sample preparation by
volatilization or precipitation.

91. • In titrimetric analysis errors may occur due to the Failure
of reactions to proceed or at completion.
• Occurrence of induced and side reactions.
• In gravimetric analysis:Decomposition or co- precipitation
and post – precipitation of constituents other than the
desired ones.

92. Contamination:
• Contamination of sample by external sources can be a
serious source of error and may be extremely variable.
• Aluminum levels in the dust in the normal laboratory are
so high that dust prohibits the determination of low ppb
levels of aluminum in samples.

93. Indeterminate errors :
Indeterminate errors can not be pin- pointed to any
specific well defined reasons.
They are random in nature & take place in several
successive measurements performed by the same
analyst under the same conditions and identical
experimental parameters.

94. Sources of random error include the limitations of reading
balances, electrical noise in instruments and vibrations
caused to the building by heavy vehicular-trafficking ,
which are beyond anyone's control.
For eg. A balance that is capable of measuring only to
0.001 g can not distinguish between two samples with
masses of 1 .0151 & 1 .0149 g.
In one case the measured mass is low, in the other case it
is high.

95. ACCURACY
• An accurate result is the one which matches very nearly
with true value of a measured amount.
• Accuracy is inversely proportional to the error i.e. the
greater the accuracy, smaller is the error.

96. PRECISION
Agreement among a cluster of experimental results
however it does not imply anything with respect to their
relation to the true value.
Precision designates reproducibility of a measurement,
whereas accuracy the correctness of a measurement.

97. Minimizing systematic errors:
• Calibration of instruments, apparatus and applying
necessary corrections:
• Instruments commonly used in lab, such as
spectrophotometer, electrical balance etc must be
calibrated before use.
• Pipettes, burettes, volumetric flasks, thermometers must
be calibrated.

98. • The response of most of the instruments changes with
time because ofwear corrosion or mishandling, etc.
• The determinate personal errors may be eliminated by
carefull practice and self discipline.

99. • The errors of method can be checked by carrying out
the analysis of standard sample prepared in such a way
that its composition is exactly the same as that of
material to be analyzed.
• For this purpose, standard materials containing carefully
analyzed constituents are available from

100. Independent method of analysis
• It is carried out to maintain accuracy of the result
• e. g. Iron (III) is first determined gravimetrically by
precipitation method as iron (III) hydroxide and then
determined titrimetrically by reduction to the iron (II)
state.

101. Performing a parallel control determination :
• Performing a separate estimation under almost identical
experimental parameters with a quantity of a standard
substance that consists of exactly the same weight of the
components as is present in the unknown sample.Can be
calculated by following expression:
• Where ,

102. BLANK DETERMINATION:
To determine the effect of impurities present in the
reagents & vessels used and where it is necessary to
locate the exact end point.
It may be accomplished by performing a separate parallel
estimation, without using the sample.

103. Cross – checking results by different methods
of analysis:
In certain specific cases the accuracy of a result may be
cross linked by performing another analysis of the same
substance by another method.
Eg. HCl –Solution : It may be assayed either by titration
with a std. sol. Of NaOH, or by precipitation and weighing
as AgCl.

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