LEC

Quality

• It is defined as the sum of ALL FACTORS which directly or indirectly contribute to the safety,
effectiveness, reliability of the product. • These properties are built into the product through research
and during the manufacturing process called “Quality Control”

Quality Control guarantees within reasonable limits:

• That the drug product is free from impurities

• Physically and chemically stable

• Contains the correct amount of active ingredients stated on the product

• The product provides optimal release of the drug

Standards for

drug product

quality

• Compendial

• Based on the USP and NF or any

other pharmacopeia or formulary

• Regulatory

• Enforced by the local Drug

Regulatory Body

• In-house

• Within the manufacturing company.

Usually goes above and beyond both

compendial and regulatory

standards.
Methods in Quantitative Chemistry

Volumetric Analysis

• Determination of the volume of a solution of known

concentration required to react with a given amount of

substance

• Uses various standard solutions, volumetric instruments

such as burets, volumetric flasks, and pipettes.

• Currently being slowly phased out to be replaced by

instrumental methods of analysis

Burette

• Graduated glass tube of uniform bore

throughout the whole length, used in

the measurement of variable

quantities

Volumetric Flask

• Calibrated to contain a precise

volume at a certain

temperature

Pipettes

• These are small tubes of glass

or plastic used to transfer the

volume indicated from one

container to another
Physicochemical Analysis

• Based on specific physical and chemical properties of

the substance being analyzed.

• Relates the physicochemical properties with the amount

of substance in the sample.

• In many cases, physicochemical properties requires the

utilization of an instrumental technique.

Chromatography

Spectrophotometric

Electrometric

Refractometric

Polarimetric

Gravimetric Analysis

• Separation by extraction, precipitation, or other means of

the constituent to be determined in the natural state or in

the form of a definite compound

Special Methods

• Require a distinct type of technique

• Examples:

• Kjeldahl nitrogen determination

• Saponification Value, Ester Values

Other Classifications of

Quantitative Method of

Analysis
Based on the analyte/s determined

or extent of analysis performed

• Complete

• Amount of all constituents is determined

• Partial

• One or more, but not all constituents are determined

• Proximate

• Determination of the percent of one or more constituents in a

sample

• Ultimate

• Means that the percent of each element in a substance is

Determined

II. Based on amount of sample used in

the analysis

• Macro

• More than 0.1g

• Semimicro

• 10-100mg

• Micro

• 1-10mg

• Ultramicro

• Less than 1mg

III. Based on the amount of analyte

present

• Major

• Analyte is present in high concentrations

• Trace Analysis

• Analyte is present in low concentrations

Sampling Securing a representative sample

Errors in analysis

Errors in analysis is categorized according to the source and

nature of errors.

Indeterminate Errors

• Slight variations in a series of observations made by the same observer under the

same conditions.

Determinate Errors

• Occurs constantly in a series of determinations

• Probable causes include

• Personal Errors

• Methodical Errors

• Apparatus Errors

Central Values

Mean/Average

• Quantity obtained by dividing the sum of replicate measurements by

the number of measurements in the set.

Median

• Middle value in a set of data that has been arranged in order of

size.

Outliers

• Outliers – Extreme values that stray off the data set.

• Example: 25,29,3,32,85,33,27,28
Precision vs Accuracy

Precision

• Measure of reproducibility within a series of results.

• Described using standard deviation, variance, and coefficient of

variation

Precision

Accuracy

• Indicates closeness of the measurement to its true or accepted value

• Indicated in degrees of error (absolute or relative

QUANTITATIVE UNITS OF CONCENTRATION

MOLE

• Simply a unit of

measurement

• Quantity of anything that has

the same number of particles

found in 12.000 grams of

carbon-12

• 1 mol = 6.02214179 ×

1023 things

MOLE

• Numerical value of things in a

mole is often called

Avogadro’s Number (NA) also

known as Avogadro constant

EXAMPLE: How many molecules are present in 2.76 mol

of H2O? How many atoms is this?

MOLAR MASS

• Molar mass is the mass of 1 mole of a compound

• Unit: grams/mole or g/mol

• To determine the molar mass:

1. Use the chemical formula to determine the number of each type of atom

present in the compound

2. Multiply the atomic weight (from the periodic table) of each element by

the number of atoms of that element present in the compound

3. Add it all together and put units of gram/mole after the number

EXAMPLE: How many moles of H2O are present in 240.0 g

of water (about the mass of a cup of water)?

MOLARITY

• Molarity (M) is the

concentration of a substance

in a solution, expressed as

the number of moles of

solute per liter of solution.

• Common unit: mol/L

• Molarity = moles of solute

liter of solution

EXAMPLE: What is the molar concentration of a solution

of 22.4 g of HCl dissolved in 1.56 L?

MOLALITY

• Molality (m) is defined as the number of moles of solute

per kilogram of solvent

• Molality = moles of solute

kilogram of solvent

EXAMPLE: Calculate the molality of a solution prepared

from 29.22 grams of NaCl in 2.00 kg of water.

• Formula of Normality in terms of Molarity

Normality = n X Molarity

EXAMPLE: Calculate the normality of NaOH solution

formed by dissolving 2g of NaOH to make 250mL

solution
Titrimetry and AcidBase Titrimetry

Titration

Titration is the slow addition one a known concentration (titrant) to a

known volume of another solution until the reaction reaches

neutralization, which is often indicated by a color change.

The solution called the titrant must satisfy the necessary requirements

to be a primary or secondary standard

Titrant

A solution of known

concentration.

Should be a primary

or secondary standard

Analyte

A substance with an unknown

concentration but with definite

volume.

Must be able to react with the

analyte in a known ratio

Indicator

A substance that changes color in response to a chemical change.

A drop of indicator solution is added to titration in the beginning

and the change of color signifies that the reaction is completed.

The indicator changes color when the reaction has reached the

equivalence point or stoichiometric point

Rules for Indicators

Use 3 drops of indicator test solution for a titration unless otherwise

directed

When a strong acid is titrated with a strong alkali, or a strong alkali

with a strong acid, MO, MR, or Phenolphthalein may be used

When a weak acid is titrated with a strong alkali, use

Phenolphthalein

When a weak alkali is titrated with a strong acid, use methyl red

A weak alkali should never be titrated with a weak acid and vice

versa, since there will not be a sharp end point.

Presence of a color is more easily observable compared to a

disappearance of a color, titrate to a color

Types of Titration

Direct Titration • The analyte reacts directly with the

titrant

Indirect Titration

• The analyte is first converted to a

secondary substance that reacts with

the titrant

Back Titration

• The analyte is treated with an excess

amount of a chemical, then the excess

will be titrated.
Primary Standardization

• A primary standard is a substance of known

high purity which may be dissolved in a known

volume of solvent to give a primary standard

solution

Primary Standard

• A standard that is sufficiently accurate that it

cannot be calibrated or subordinate to other

standards.

• In chemistry, it is a reagent that can be weighed

easily and which is so pure that its weight is

truly representative of the number of moles in

the substance contained.

• Properties: High Purity, Stable, Low

hygroscopicity, High Equivalent Weight, Nontoxic, Cheap

Samples of Primary Standards

• Sodium Carbonate, Sodium Tetraborate,

Potassium Hydrogen Pthalate

• Pure metals and salts

• Silver Nitrate, Sodium Chloride, Potassium

Chloride

• Potassium Dichromate, Potassium Bromate,

Potassium iodate, Sodium Oxalate, Pure Iron

Secondary Standard

• A secondary standard is a chemical that has

been standardized against a primary standard

for use in specific analysis. Secondary standards

are commonly used to calibrate analytical

methods

• 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 reacting of a

volume of the solution against the measured

volume of a primary standard solution.

Titer

Defined as the weight of a substance

chemically equivalent to 1mL of a

standard solution.

1mL of 1N HCl contains 0.03646 g of HCl

and is therefore equivalent to 0.04000g

of NaOH

Titers of standards solutions used in

official assay procedures are specified in

various monographs.

Assay of Ca(OH)2

solution: Each mL of 0.1N HCl is equivalent to 3.705mg of

Ca(OH)2

Types of Reactions Used in Titrimetry

 Neutralization (Acid-Base)
 Oxidation-Reduction
 Precipitation
 Complexation
Principles of Neutralization Titrations

MCDM

Titration Curve

• A titration curve is a plot of some function of the analyte or titrant

concentration on the y-axis versus titrant volume on the x-axis

• To understand the theoretical basis of end-point determinations and the

sources of titration errors, calculate the data points necessary to construct

titration curves for the systems under consideration

Types of Titration Curves

First type, called a sigmoidal curve, in which the p-function of

analyte (or sometimes the titrant) is plotted as a function of titrant

volume

Second type of curve, called a linear segment curve, the vertical

axis represents an instrument reading that is directly proportional to

the concentration of the analyte or the titrant

• The sigmoidal type offers the advantages of speed and convenience. The linear

segment type is advantageous for reactions that are complete only in the presence

of a considerable excess of the reagent or analyte.

Concentration Changes During Titrations

• The equivalence point in a titration

is characterized by major changes

in the relative concentrations of

reagent and analyte

Standard Solutions

The standard solutions used in

neutralization titrations are strong

acids or strong bases because these

substances react more completely

with an analyte than do weak acids

and bases, and as a result, they

produce sharper end points.

Standard Solutions

The standard solutions used in

neutralization titrations are strong

acids or strong bases because these

substances react more completely

with an analyte than do weak acids

and bases, and as a result, they

produce sharper end points.

Standard solutions of acids are

prepared by diluting concentrated

hydrochloric, perchloric, or sulfuric

acid