Pharmaceutical Analysis Basics

8/10/2019 Pharmaceutical Analysis Basics

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Pharmaceutical Analysis 62

Pharmaceutical Analysis

Definition:Chemical Analysis is a method for determining the substance, its amount or impurity and

plays a vital role in the pharmacy.

Analytical chemistry Methods

1. Qualitative analysis

2. Quantitative analysis

Qualitative or physical analysis

Recognition of chemical species by means of:

Colour, taste, Viscosity and solubility

Reaction producing a colour

Reaction producing a precipitate

Reaction involving a change of a physical parameter.

Quantitative chemical analysis

Quantitative chemical analysis carried out by determining the volume of a solution of accurately

known concentration which is required to react quantitatively with a measured volume of the

substance to be determined.

Classification

1. Neutralisation Reactions

2. Complex Formation Reactions

3. Redox Reactions

4.

Precipitation Reactions

Basicsand definitions

A solution:

Is a homogeneous mixture composed of two or more substances. In such a mixture, a solute is

dissolved in another substance, known as a solvent.


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Concentrations:

Is a measure how much of given substance there is mixed with another substance

most frequently the concept is limited to homogeneous solutions, where it refers to the amount

of solute in a substance.

Standard solution:

Is a chemical term which describes a solution of known concentration.

The concentration of the solution is normally expressed in units of moles per Liter (mol/L,

often abbreviated to M for morality).

Standard solutions are normally used in titrations to determine the concentration of a substance

in solution.

A molar solution:

Is one that contains one mole of solute (molecular weight) per liter of solution.

For example:

A five molar solution of aqueous hydrochloric acid (written as "5M HCl (aq)") means there

are 5 moles of HCl per liter of solution

If one liter of a solution contain 98 g of H2SO4, this means that the concentration is 1M

If one liter of a solution contain 98x2 (196) g of H2SO4, this means that the concentration is

2M

Normal solution:

Is one that contains one equivalent weights of solute per liter of solution.

For example:

A five normal solution of aqueous hydrochloric acid (written as "5N HCl (aq)") means there

are 5 equivalents of HCl per liter of solution

Calculation of equivalents:

1. For acids:

One equivalent of an acid is that amount of an acid that will furnish one mole of hydrogen ions

or that will react with one mole of hydroxide ions.

mL

meqno.

L

eqno.

solutionofliter

soluteofweightsequivalentofnumberNormality ===


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To calculate the equivalent weights of acid =

To calculate the equivalent weights of base =

Example: the molecular weight of HCL is 36.5 g and contain one mole of hydrogen ions that

will react with one mole of hydroxide ions:

The equivalent weights of HCL is 36.5/1 = 36.5

The molecular weight of H2SO4 is 98 and contain two mole of hydrogen ions that will react

with one mole of hydroxide ions:

The equivalent weights of H2SO4is 98/2 = 49

The molecular weight

Number of H ions

2. For bases:

one equivalent of a base is that amount of a base that will furnish one mole of hydroxide ions

or react with one mole of hydrogen ions.

The molecular weight

number of OH ions

Example: NaOH + HCL NaCL + H2O

The molecular weight of NaOH is 40 and contain one mole of hydroxide ions that will react

with one mole of hydrogen ions:

The equivalent weights of NaOH is 40/1 = 40

Al(OH)3+ 3HCL ALCL3+ H2O

The molecular weight of Al(OH)3is 87 and contain three mole of hydroxide ions that will react

with three mole of hydrogen ions:

The equivalent weights of Al(OH)3 is 78/3 = 26

3. For Salts:

one equivalent of a salt is that amount of a Salt that will result from replacement of one mole of

hydrogen ions of conjugated acid .

NaOH + HCL NaCL + H2O

The molecular weight of NaCL is 58.5 and result from replacement of one mole of hydrogen

ions of conjugated acid HCL.

The equivalent weights of NaCL is 85.5/1 = 85.5


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H2CO3 HCO3-+ H+

The molecular weight of NaHCO3is 84 and result from replacement of one mole of hydrogen ions

of conjugated acid H2CO3

The equivalent weights of NaCL is 84/1 = 84

Na2CO3:

The molecular weight of Na2CO3is 106 and result from replacement of two moles of hydrogen ions

of conjugated acid H2CO3

The equivalent weights of NaCL is 106/2 = 53

1. Neutralisation Titrations

(acid - base titration)

Acid base titration terminology:

Titration

A process in which a solution of one reactant, the titrant, is carefully added to a solution of

another reactant, and the volume of titrant required for complete reaction is measured.

Equivalence point

The point at which stoichiometrically equivalent amounts of an acid and base have reacted.

Indicator

A compound that exhibits its different colors in solutions of different acidities. Used to determine

the point at which an acid-base reaction is complete. (phenolphthalein)

End point

The point at which an indicator changes color and a titration is stopped. The end point should

coincide with the equivalence point

Acid base titration

The neutralisation reactions between acids and bases used in chemical analysis.

These reactions involve the combination of hydrogen and hydroxide ions to form water.

Ex:

NaOH + HCL NaCL + H2O


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To perform neutralisation titration is necessary to have a solution of base for example at known concentration a glass

vessel, a burette (calibrated tube able to measure volume, equipped with a tap) and an indicator (chemical species able to

change colour when change the composition of the solution.

The standard solution for the titration must be strong base or acid(for complete dissociation and

reaction)

Weak acids and bases dissociate and react partially so can not be used by titration as standard

reagent.

Ex:

NH4OH + HCL NH4CL + H2O

NH4OH dissociates partially in a solution into (NH4OH NH4+ + H2O). Thus by

titration ammonia ions will be not consumed by reaction with HCL and still free.

Color change of the indicator will appear only if the whole chloride ions are consumed.

Requirements of standard reagents:

1. Not volatile and stable

2. Complete dissociation and ionization

Change of pH


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3. Have no oxidation properties (to prevent oxidation of indicator)

4. Are not insoluble salts because this make detection of end point difficult.

Types of acid- base titration:1. Non-Aqueous

Take place in a solvent other than water (Glycerin, Polyethelene glycol, alcohol)

Used for weak substances which dissociate partially in water making difficulties in

determining change of pH

Called non aqueous titration

Ex: CH3COOH CH3COO-+ H+

2. Aqueous

Take place in water

Used for substances which dissociate completely and rapidly in water

Determination of change of pH is easy

Called aqueous titration

Requirements of indicators:

1.

The change of color is at equivalent point is clear

2. Not volatile

3. Chemically inert

4.

Do not form insoluble complexes

pH Indicators

1. are organic dyes with either acid or basic character

2.

are organic dyes that change their colour on acceptance or release of protons

3.

are used for rapid determination of an endpoint in an acid-base titration

4. are used for the quantitative determination of a given acid or base content of a solution

5. does not change the colour immediately but continuously within a given pH range

Application of acid base titrations in pharmacy :

Salicylic acid

Benzoic acid


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General law used in calculations of neutralization titrations:

Example:

NaOH Solution, Volume = 200 ml, concentration = 0.1 N

Calculate the weight of NaOH in the solution?

No. of eq. = V x N

No. of eq. = 200/ 1000 x 0.1 = 0.02 Equivalents

1 Equivalent 40 g

0.02 Equivalents Xg

Xg = (40 x 0.02)/ 1 = 0.8 g

No. of equivalents in a solution = Volume of the solution x Normality

No. of eq. = V x N


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2.Precipitation Titrations Titrations between analytes and reagents resulting in the formation of a precipitate.

The most useful of these precipitating reagents is silver nitrate AgNO3.

Titrimetric methods based upon the use of silver nitrate are sometimes called Argentometric

titrations.

Used for the determination of many anions including:

1. Halides: Br-, CL-, I-

2. Divalent anions S2-

3. Mercaptans CH3SH

4. Certain fatty acids

Ex: HCL + AgNO3 AgCL + HNO3

The precipitate will begin to form as the reaction take place and the end point will be determined

at the end of reaction (after completion of precipitate)

Endpoint determination is by coloured indicators (usually back titrations) or turbidity methods.

Examples of solutions used in precipitation titrations

1.

Silver nitrate AgNO3:

For titration of Br-, CL-, I-and CN-

HCL + AgNO3 AgCL + HNO3

2. Potassium thiocyanate KSCN:

For titration of Ag+as AgSCN and Hg2+as Hg(SCN)2

KSCN+ Ag+ AgSCN

KSCN+ Hg2+ Hg(SCN)2

3. Potassium cyanate KCN:

For titration of Copper Cu and Nickel Ni

4. Hg(NO3)2Mercury(II) nitrate:

For titration of Copper Cl-, Br-, I-, SCN-


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Methods used for determination of equivalence point in precipitation titrations:

1. Mohr method

The chromate ion is employed as an indicator in the Mohr method.

Sodium chromate can serve as an indicator for the argentometric titrations of chlorine,

bromine and cyanide ions, by reacting with silver to form silver chromate (Ag2CrO4).

Red Ag2CrO4(s) precipitates when excess Ag+rapidly increases near equivalence and thus is

a useful indicator.

The Mohr method will follow these reactions:

Ag+ + Cl- AgCl (s) white

2Ag+ + CrO4-2 Ag2CrO4(s) red

2. Volhard method

The indicator used in the Volhard method is Iron(III) ion

In this method, silver ions are titrated with a standard solution of thiocyanate ion, where Fe 3+

serves as the indicator imparting a red color to the solution.

The most important application of the Volhard method is for determing the presence of halide

ions. An excess of silver nitrate is added to the sample and back-titrated with a standard

thiocyanate solution.

The reaction that accompany the Volhard method are:

Ag+ + Cl- AgCl (s) white

SCN- + Ag+ AgSCN (s) white

Fe3+ + SCN- Fe(SCN)2+ red

3. Fajans method:

The indicator used in the Fajans method is Flourescein (an adsorption indicator)

An adsorption indicator is an organic compound that tends to be adsorbed onto the surface

of the solid in a precipitation titration.

In the ideal scenario, the adsorption occurs near the equivalence point and results in a color

change.

The endpoint is noted by a change in color from fluorescent green to light pink.


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Flourescein structure

Application of precipitation titration used in pharmacy:

Determination of presence of metals in some solutions or some pharmaceutical dosage forms

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Because EDTA complexes most cations, the reagent might appear at first glance to be totally

lacking in selectivity

However, great control can be acheived by pH regulation and the selection of suitable indicators

Indicators in complexometric titrations:

Are organic complexe builders

Build specific coloured metal ion complexes

Used for detection of equivalent point in complexometry

Typical indicators are:

- Murexide

- Solochrome black

- Calmagite

- Bromopyrogallol red

- Xylenol orange


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Typical applications:

1. Determination of cations

2. Hardness of water

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A reduction occurs when an atom or ion gainselectrons

Example:

Potassium Permanganate: MnO4-+ 8H++ 5e- Mn2++ 4H2O (reduction) x 2

Iodine: 2I- I2+ 2e- (oxidation) x 5

2MnO4-+ 16H++ 10I- 2Mn2++ 8H2O + 2I2

Indicators in Redox titrations:


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Typical applications:

1. Pharmaceuticals - Vitamin C determination

2. Determination of amount of iron in its raw material

3. Iodine determination

Instrumental Analysis

1. Spectrophotometer

2.

Fluorescence

3.

Flame photometer

4. Atomic absorption

5. Electrophoresis

6. Infra red

7. Polarometer

8. Mass Spectroscopy

9. TLC (Thin layer chromatography)

10.GC (gas chromatography)

11.HPLC (High performance liquid chromatography)

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Pharmaceutical Analysis Basics