MODULE 2:

General Directions in Quantitative

Analysis
Learning Objectives
• ​Acquisition of fundamental knowledge on theories
and practical abilities in the application of
analytical methods.

• ​Determine what reactions are taking place during

an analysis and be able to understand and apply the
theory upon which the method is dependent.

• ​Acquisition of skills in technique, patience,

neatness and accuracy.
*Analysis is carried out not for the sake of analysis
but as a means of controlling strength and purity of
substances used as medicaments.
Characteristics of an Analyst
• ​Aside from common sense and critical
thinking for each procedure, the analyst
must:

– ​Avoid slight loss or gain of material under

analysis or extraneous matter.

– ​Possess honesty and integrity.

– ​Ability to determine if the method is worth of

 full confidence.

– ​Have the initiative to perform at least two

determinations of the analytical value.
Economy of Time

– ​Preliminary study of the work to be done

is a must, followed by a plan for its prompt
execution.

– ​There is no such thing as speed in

quantitative work.

– ​Economy of time is achieved not by haste

 but by planning the work so that
operations may run parallel at the same
time.
Guidelines in Maintaining Economy of
Time and Accuracy
– ​Keep the desk clean and organized at all
times.
– ​Clean all apparatus immediately after
using it and put it in designated places.
– ​Label all solutions, filtrates and
precipitates systematically throughout the
analytical procedure.
– ​Keep two or more operations going at one
time.
 – ​Utilize all time between operations in
making calculations and documentation.
Basic Needs for Quantitative Work
Cleaning Solution for Glasswares and Porcelain
Wares
Prepared by dissolving sodium dichromate in
100mL of water and then adding 1,500mL sulfuric
acid slowly with stirring.

Wash Bottles
Usually consist of rubber-stoppered, flat-bottomed
flasks of 500 to 1,000mL capacity fitted with
smoothly bent tubes and a jet made flexible by
 means of a rubber joint, should deliver an even
stream of liquid.
Basic Needs for Quantitative Work
Policeman
A piece of soft rubber tubing fitted to the end of a
glass rod used to loosen adhering particles from
the walls of containing vessels, that are not
removable by a stream of water from the wash
bottle.

Reagents
Must be pure
Must conform with USP/NF requirements
Reagents labeled as “analyzed” or “reagent”
 grade and those that meet the specs of the
American Chemical Society meet all official
requirements.
Basic Needs for Quantitative Work

Purity and Strength Requirements

Are usually expressed in terms of percent
Conformity with these requirements can only be
established if official methods of assay are
employed.
Sampling
– ​Process of removing an appropriate number of
 items from a population in order to make
inferences of the entire population.
– ​If possible and feasible, a sample from each
package should be examined separately. ​– ​When
a single package is to be sampled, the contents
should be mixed or should be taken ​from
different parts of the container and mixed ​and
then a portion of this mixture should be taken
for analysis.
– ​Samples that require drying should be spread on
a large watch glass, thoroughly mixed, and dried
in an oven at the specified temperature and
should be then transferred to a weighing bottle
and kept in the dessicator.
Results and Errors
– ​Duplication of results are not an assurance of
 accuracy since errors inherent in the method
employed maybe repeated.

– ​Results that agree closely when obtained by two

different methods of analysis is a good indication of
the reliability of methods.

– ​In general, results of repeated analysis or

measurements will fail to agree when made by the
same analyst or by different analysts to the full
precision the method or the instrument is capable.

– ​Hence, all experimental data are subject to

discrepancies due to the various sources of
errors.
Indeterminate and Determinate Errors
Indeterminate Errors
– ​Manifest themselves by slight variations in a
series of observations made by the same
observer under identical conditions.
– ​Causes are difficult to detect, intangible and
,their elimination by the analyst is
impossible.

Determinate/Systematic Errors
– ​Recur in a constant manner in each of a series
of determinations.
– ​Detectable and hence, it is possible to eliminate
 or reduce their effect on the final result.
Examples

Indeterminate Errors
– ​Judgment, skill, and attitude of the analyst.

Determinate Errors
– ​Personal errors such as inability to judge color
changes sharply
– ​Faulty procedure such as incorrect sampling,
contamination, improper selection of indicators
– ​Apparatus errors due to poor construction or
calibration
 Accuracy
– ​Used to denote the agreement of an experimental
data or the mean of a series of data with the true
value.
– ​If the true value is not known, the mean calculated
from results of several methods that are very close
to each other maybe considered the true value.

*Absolute Error
– ​Difference between the mean and true
value *Relative Error
– ​Obtained by dividing the absolute error by the true
value
– ​Reported on a percentage basis or parts per
 thousand basis
Precision
– ​Measure of reproducibility of data within a
series of results.
– ​Measures how close the data agrees with each
other.
– ​Precise results are not necessarily accurate
since a determinate error maybe responsible
for inaccuracy of each result in a series of
measurements.
– ​Reported as average deviation, standard
deviation and range.
Precision Reporting: Average Deviation
– ​Obtained by finding the individual differences of the
results from the mean. The differences, regardless of sign,
are then added and divided by the number of
determinations.
* Dividing the average deviation by the mean shall give the
relative average deviation, expressed in percent or parts
per thousand.
Example:
Four separate titrations of NaOH solution yielded the
following normality values:
0.2140N, 0.2142N, 0.2152N, and 0.2146N
Mean (​Χ​):
0.2140N + 0.2142N + 0.2152N + 0.2146N
4
= 0.2145N
Average Deviation
0.2140N – 0.2145N = 0.0005N
0.2142N – 0.2145N = 0.0003N
0.2152N – 0.2145N = 0.0007N
0.2146N – 0.2145N = 0.0001N

Average Deviation (​d​):

0.0005N + 0.0003N + 0.0007N +
0.0001N​ ​4
= 0.0004N

Relative Average Deviation

(​d/X​): ​0.0004N ​x 100 = 0.19%
0.2145N
Standard Deviation
• More preferred measure of precision than average
 deviation.
• Computed by:
_________
​
√∑ (​Xi​ –​ ​X)2​ /(n-1)
* Dividing the standard deviation by the mean ​shall give the
relative standard deviation, expressed in percent.
Example:
Standard Deviation (​s)​ ​:
__________________________________________
√ ​(0.0005N)​2 ​+ (0.0003N)​2 ​+ (0.0007N)​2 ​+ (0.0001N)​2
4-1
= 0.0005N ​s/X =​ ​0.0005N​ x 100 = 0.23% 0.2145N
Range of Values which probably includes the True
Value: ​0.2145N plus/minus 0.0005N = 0.2140N to
0.2145N

Range
• The difference between the largest and smallest
results in a series of measurements.
Example:
Range (​R​):
0.2152 – 0.2140 = 0.0012
Rejection of a Result
– S​ ometimes, one result differ greatly from the
other analytical values although there are no
apparent mistakes.
– ​If at least four determinations have been
made, the result in which the error appears to
be large maybe rejected when its deviation is
 four or more times than the average deviation
of the other values from the mean.

Example:
Five determinations of chloride in a NaCl sample
yielded the following percent purities: 95.72%,
95.81%, 95.83%, 95.92% & 96.18%
Rejection
(​X​) of the first four values:
95.72% + 95.82% + 95.83% + 95.92%
4
= 95.82%

95.72% – 95.82% = 0.10%

95.82% – 95.82% = 0%
95.83% – 95.82% = 0.01%
95.92% – 95.82% = 0.10%

d ​= 0.05%

Deviation of the last value(96.18%-95.82%) =

0.36% 0.36%/0.05% = 7.2
General Operations: Crucibles
– ​High-grade porcelain crucibles are the
most commonly employed materials in
practice, since they withstand high temp
and are suitable for use in the ignition of
most drugs and precipitates.
– ​They are not suitable for fusions, since the
flux attacks the glaze.
– ​Other materials employed for crucible
construction are fused silica, alundum,
nickel and platinum.
 *Gooche Filtration Crucible
– ​Special crucible with a perforated bottom
upon which is bedded a mat of asbestos
making it possible to collect, wash, dry, and
weigh a precipitate in the same crucible.

Fritted Glass Crucibles

– ​Have fused-in sintered or fritted glass
bottoms that come in ​medium ​and
fine ​porosities.
– ​Medium porosity-sintered glass
bottoms are suitable for flocculent
and moderately fine precipitates.
– ​Fine porosity-sintered glass bottoms
are suitable for fine precipitates
especially sulfides.
– ​Such crucibles are useful in
 procedures that require the residue
to be dried to constant weight at
temperatures below 150​o​C.
– ​Heating should be done in an oven
and are allowed to cool to room temp
in a desiccator.
General Operations: Filtration and Washing
of Precipitates
– ​The most usual and efficient method of washing a
precipitate is by decantation for about 3 or 4 times
accompanied by vigorous stirring.
– ​The precipitate is further washed by filtration with
the residue treated by a fine stream of running
water from a wash bottle, top edge to bottom of
the filter.
– ​The filter should be about ¾’s full of the washing
 liquid.
– ​The rinsing is discarded and repeated only until the
filter is empty of the washing liquid.
– ​The filtrate is tested for completeness of washing
after about five repetitions.
General Operations: Colloidal and Fine
grained Precipitates

– ​Colloidal and gelatinous precipitates are converted

into dispersions by water which pass through
filters.

– ​These substances can only be filtered by boiling

them with NH​4​NO​3​, NH​4​Cl or HCl with suitable
 wash liquors.

– ​The precipitating agent in such cases should be

added slowly to prevent supersaturation, that may
lead to formation of fine crystals.
General Operations: Evaporation of Liquids
– ​Porcelain dishes that expose a large surface area of
the liquid to the air should be used.

– ​Most evaporations should be carried out in a

water bath to avoid decomposition and loss of
material.

– ​The dish should be covered by an inverted funnel

or with a watch glass elevated by a glass triangle to
 avoid entry of extraneous matter.

– ​Large quantities of liquids are best evaporated in a

small dish by adding fresh portions of the original
liquid from time to time to replace lost liquids.
General Operations: Transfer of Liquids

– ​Few transfers as possible should be made.

– ​After transfer, the original container should be

washed with successive small portions of wash
liquid, with the washings added to the receiving
container.
 – ​A glass rod should always be used and held tightly
against the lip of the original container, while the
other end should touch the wall of the receiving
container.
General Operations: Drying and Ignition of
Samples and Precipitates
– ​Many procedures call for drying under specified
conditions before analysis to correct for moisture.
– ​Electrically-heated ovens best suits analytical
procedures since its temp is constantly
controllable.
– ​Samples should be dried at the specified temp on
a watch glass or in a suitable container.
– ​Precipitates on filter papers maybe dried directly
 using an oven and the filter paper must be held in
place by crimping its edges over the funnel.
Temperature for such procedures should be
90- 100​o​C unless otherwise specified.
Ignition Guidelines
– ​Samples maybe ignited without drying unless otherwise
specified.
– ​The precipitate is folded within an ashless filter paper
and placed in a crucible.
– ​Moisture is driven off by intermittent application of flame
while the crucible is covered, until the filter paper is well
charred.
– ​The cover is then removed and the crucible inclined on a
clay triangle and the full flame turned on until all carbon
has been burned away. The crucible is rotated slightly
from time to time.
– ​The crucible with the ignited residue is allowed to cool in
 a desiccator and weighed.
– ​It should be ignited again and weighed. If the successive
weighings do not agree within 0.2mg, if a porcelain
crucible is used, a third repetition is required until
constant weight is attained.
Constant Weight
– ​Official methods often direct that a drug be dried
to constant weight, which means that two
consecutive weighings do not differ by more than
0.5mg/g of substance taken for determination. The
second weighing should be done after an
additional hour of drying.

– ​In analytical procedures though, the sample is

heated at the specified temp, cooled and weighed,
and is reheated, cooled and again weighed. If the
 two weighings agree within 0.2mg, constant
weight is said to have been reached. If the change
in weight is more than 0.2mg, the process of
heating, cooling and weighing is repeated until
constant weight is obtained.
General Operations: Desiccators
– ​Special forms of glass vessels, rendered airtight
to maintain a dry atmosphere for objects that
might be affected by moisture or CO​2​.
– ​If surfaces in contact with the cover are not
airtight, a coat of grease prepared by melting
beeswax and petrolatum maybe applied onto
contact surfaces.
– ​Must have two compartments, separated by a
 perforated porcelain or glass plate.
– ​The glass plate is for holding the crucibles or
samples while the lower compartment is for
containing the dehydrating agent, usually silica
gel, anhydrous CaCl​2​, solid KOH, P​2​O​5​, or
Mg(ClO​4​)​2
Some Important Guidelines in the Use of
Analytical Balances
– ​Carelessness of one may render inaccuracy of
all. ​– ​The pan and floor of the balance should be
brushed before and after weighing.
– ​Samples should not be directly placed over the
balance pan. Solids are weighed by using a
weighing bottle or watch glass, and liquids are
 weighed by using a dropper bottle.
– ​Hot objects to be weighed must be allowed to cool
first.
– ​Spillage must be brushed or cleaned at once. ​–
When a substance is directed to be ​accurately
weighed ​for an assay, error is limited to 0.1% or
less.