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PHARMACEUTICAL

ANALYTICAL CHEMISTRY

Dr. Ahmad Najjar

0510113

Philadelphia University Faculty of Pharmacy

Department of Pharmaceutical Sciences First Semester, 2017/2018

CHAPTER 1

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ANALYTICAL OBJECTIVES

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ANALYTICAL CHEMISTRY /

PHARMACEUTICAL ANALYSIS

Analytical chemistry is the study of the separation,

identification, and quantification of the chemical

components of natural and artificial materials.

Pharmaceutical analysis is the application of the

knowledge of analytical chemistry to analyze

pharmaceutical raw materials or finished products

where the principle of analytical chemistry is applied

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Analytical science deals with the chemical

characterization of matter—what, how much?

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Qualitative and Quantitative Analysis

The analyst must know what information is really

needed, and obtain a representative sample.

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ANALYTICAL CHEMISTRY

1- Qualitative Analytical chemistry:

- Focuses on the presence or absence of analyte

- Identification of analyte

- Recognized by color, boiling point, solubility, taste,… etc.

2- Quantitative Analytical Chemistry:

- Determination of concentration

- Gravimetric or titrimetric measurements, or instrumental

methods used are depending on physical properties

measurements like conductivity, electrode potential, light

emission absorption, mass to charge ratio, fluorescence, and

many more…

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Quantitative Analytical methods are classified

according to the final measurement step into:

• Volumetric methods (volume)

• Gravimetric methods (weight)

• Instrumental methods (absorbance, optical rotation, etc…)

Quantitative Analytical methods

Few measurements are specific, so operations are

performed to achieve high selectivity.

You must select the appropriate method for

measurement.

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QUANTITATIVE ANALYTICAL METHODS

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inst

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enta

l

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THE ANALYTICAL PROCESS

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LABORATORY TOOLS

Volume measuring

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Read from meniscus at

eye level

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LABORATORY TOOLS

Filtration

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LABORATORY TOOLS

Temperature measurements

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LABORATORY TOOLS

Weighing

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Analytical balance

Top loading balance

Triple beam balance

Spatula Weighing boats

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CHAPTER 5

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Learning Objectives

● How to calculate molarities and moles

● How to express analytical results

● How to calculate weight and percent analyted from molarities, volumes, and reaction ratios

● Weight relationships for gravimetric analysis

STOICHIOMETRIC CALCULATIONS

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Revision of basic

concepts

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Review of elementary concepts and mathematical

calculations

Main laboratory techniques: weighing, volume

measurements, drying, solutions preparation,

decantation

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SI measuring units

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MOLAR MASS

It is the mass of one mole of substance, it is called:

Molar mass, M.wt. or f.wt. , its unit is (g/mol) or (mg/mmol)

Molar mass is calculated from the atomic masses of individual atoms

composing the molecule.

KMnO4?

NaOH?

CH3COOH?

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MOLE

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1 Mole of molecules ≡ avogadro’s num. of molecules ( avogadro’s num. = 6.02x1023 )

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MOLE

also moles of substance = mass of substance / M.wt

e.g. 36 g of H2O contains

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OH mol 2g/mol 18

g 362

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Example (a) How many glucose molecules are in 5.23 g of C6H12O6?

(molar mass is 180.0 g/mol)

(b) How many oxygen atoms are in this sample?

(a) Firstly, calculate the number of moles then calculate the

number of molecules from the number of moles

(b) Each molecule of glucose has 6 atoms of oxygen, therefore

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Answer

2223 1075.16.022x100.0291

no. sAvogadro'moles ofnumber molecules ofnumber

mol 0.0291180

5.23

massmolar

massmoles

2322 101.05101.756

moelcules glucose ofnumber 6atomsoxygen ofnumber

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MOLE AND RATIO OF ATOMS IN THE

MOLECULE

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e.g. Glucose C6H12O6 the atomic ratios between C:H:O is 6:12:6

Q. 3 moles of Fe2O3 contains ? mole of Fe atoms and ? mole of O atoms.

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MOLE AND STOICHIOMETRY

e.g. Ca(OH)2Ca2+ + 2OH- , the ratio between Ca(OH)2:Ca2+:OH- is 1:1:2

Q. If we have 5 moles of Ca(OH)2, how many moles of OH will produce?

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Stoichiometry is

the ratio between substances in the balance chemical equation

Q. If you have this equation,

so how many sandwich could you make by 10 slices of bread

and 10 slices of cheese?

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substance) solid isA ifgenerally used is (thisA of massMolar

A of mass A of Moles

solution) ain substance solute isA ifgenerally used is (thissolution of Volume A ofion concentratMolar A of Moles

substance) gaseous isA ifgenerally used is (thiseTemperatur )R(constant

Volume Pressure A of Moles

known) isA ofnumber ifgenerally used is (this(constant)Number sAvogadro'

particlesA ofNumber A of Moles

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CONCENTRATION

Concentration is “The amount of a substance per defined space”

We refer to the chemical species that we are looking for its concentration by

“Analyte”, “Constituent”, “Substance”, or “Solute” while the space is called

“Sample”, “Solution”, “Mixture”, “Matrix”, “Medium” or “Solvent”

The most known concentration unit in stoichiometric calculations is the molar

concentration c and it is usually called molarity M.

Molarity (M) unit [used for solutions and it measure moles of solute per liters of solution]

Molarity = moles of substance / volume of solution (L)

M = mol / v

Q. Calculate the molarity of Cl- in a solution made by dissolving 20 g of BaCl2

in 360 mL water? (M.wt of BaCl2 is 208 g/mol)

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CONCENTRATION

Solution Preparation steps

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(M.wt. AgNO3 is 169.9 g/mol)

(M.wt. Na2SO4 is 142 g/mol)

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For solutions also we can use the unit of g/mL or g/L or mg/L to express the mass of solute per volume of solution (mass concentration p )

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CONCENTRATION UNITS

M.wtMor (L)solution of volume

(g) solute of mass(g/L)ion concentrat

(At.wt. K is 39.1 g/mol)

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CONCENTRATION UNITS

(M.wt. NaCl is 58.4 g/mol)

Normality (N) unit

Although molarity is widely used in chemistry, some chemists use a unit of concentration in quantitative analysis called normality (N).

A one-normal solution contains one equivalent per liter. An equivalent represents the mass of material providing Avogadro’s number of reacting units. A reacting unit is a proton or an electron. The number of equivalents is given by the number of moles multiplied by the number of reacting units per molecule or atom; the equivalent weight is the formula weight divided by the number of reacting units (n).

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CONCENTRATION UNITS

(eq/mol)n

(g/mol)weight Molecular (g/eq) weight equivalent

molesn(g/eq) weight equivalent

(g) mass (eq) sequivalent of No.

Molarityn(L)solution of Volume

(eq) sequivalent of No.(N)Normality

Reacting units (n), • For acids and bases, the number of reacting units is based on the number of protons

(i.e., hydrogen ions) an acid will give or a base will react with. • For oxidation–reduction reactions it is based on the number of electrons an oxidizing

or reducing agent will take on or supply. • For most of ionic reactions it is based on the charge of the cation or anion.

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CONCENTRATION UNITS

Molality (m ) unit • A one-molal solution contains one mole per 1000 g of solvent.

• The molal concentration is convenient in physicochemical measurements of the colligative properties of substances, such as freezing point depression, vapor pressure lowering, and osmotic pressure because colligative properties depend solely on the number of solute particles present in solution per mole of solvent.

• Molal concentrations are not temperature dependent as molar and normal concentrations.

(kg)Solvent of Mass

(mol) moles of No.(m)Molality

• Density (D) is the mass (g) of one unit of the solution (generally mL or L) Dr. Najjar 17/18

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Dilution is a process in which we decrease the concentration of a

substance from high concentration (initial) to lower concentration

(final) by adding more solvent.

Number of moles is not changed, only the concentration and

volume are changed, therefore

Moles initial = Moles final

(Conc. x Vol) i = (Conc. x Vol) f

Example What will be the volume of 0.2M NaCl solution that should be taken to

prepare 5L of 0.004M NaCl solution?

Answer Initial: Conc. = 0.2M, Vol.=??

Final: Conc. = 0.004M, Vol.=5L

(M.V)i=(MV)f 0.2xVi = 0.004x5 Vi = (0.004x5)/0.2 = 0.1 L

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Dilution

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Dilution steps

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Dilution

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Dilution

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Dilution

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Percentage unit ( % )

Percentage unit is a concentration unit generally used for solid

media. It could be expressed as

Q. What is the percentage concentration (%w/w) of NaCl in a solution

made by dissolving 20.0 g NaCl in 200 mL water?

Q. Calculate the Na %w/w in the above solution? (M.wt. NaCl is 58.5

g/mol and At.wt. for Na is 23 g/mol)

Q. What is the molar concentration (M) of Glucose solution that has

%w/w of 15%? (M.wt. for glucose is 180 g/mol)

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Concentration units

100(mL) sample of volume

(mL) solute of volume%

100(mL) sample of volume

(g) solute of mass%

100(g) sample of mass

(g) solute of mass%

v/v

w/v

w/w

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Example

Calculate the molarity of concentrated HCl solution that have a density of

1.188 g/mL and have % concentration of 36% w/w? (M.wt. HCl = 36.5 g/mol)

Answer

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Concentration units

11.72M1

11.72

(L)solution of volume

HCl molM then HCl, mol 11.72 containssolution theof 1L So

HCl mol 11.72g/mol 36.5

g 427.68

HCl M.wt.

HCl mass toequal moles of no. contains HCl of mass this

HCl g 68.427100

361188 HCl of mass so HCl, of 36% hassolution of mass this

g 1188 mL 1000 1.188g/mL mass volumeDensitymass

volume

massDensity , g 1188 of mass a hassolution theof 1L

(L)solution of volume

HCl of mole edconcentrat HCl ofMolarity

HCl

M 11.7236.5

361.1881000

M.wt.

%D1000M rds,another woin w/w

HCl

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Dilution

(M.wt. H2SO4 is 98.1 g/mol)

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Part Per Million (ppm) and Part Per Billion (ppb) Units

These units could be used either if the solute was present in solid, liquid or

gas medium

%o = [mass of substance (g) / mass of solution (g)] x 103

ppm = [mass of substance (g) / mass of solution (g)] x 106

ppb = [mass of substance (g) / mass of solution (g)] x 109

ppt = [mass of substance (g) / mass of solution (g)] x 1012

- we can convert molarity to ppm if

we knew the density of the solution.

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Concentration units

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Concentration units

Final thing, reporting concentrations as different chemical species

We may express results in any form of the analyte. This is often done to facilitate the interpretation by other professionals. Water hardness due to calcium ion is

expressed as ppm CaCO3. Dr. Najjar 17/18

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Concentration units

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HOW DO WE MAKE STOICHIOMETRIC

CALCULATIONS?

Chemical analysis is mainly employ the use of a balanced chemical

reaction.

In Volumetric or titrimetric analyses, the test substance Analyte (the

substance that we need to determine its concentration) reacts with

an added reagent of known concentration (standard solution). This

standard solution is typically delivered from a buret, therefore it is

called Titrant. Analyte concentration could be calculated from the

chemical relation between these two reactants.

In Gravimetric analyses, the Analyte is converted to a precipitated

Product according to a balanced chemical reaction. Analyte

concentration could be calculated from the chemical relation

between the analyte reactant and the precipitated product.

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HOW DO WE MAKE STOICHIOMETRIC

CALCULATIONS?

The requirements of a titration are as follows:

1. The reaction must be stoichiometric. That is, there must be a well-

defined and known reaction between the analyte and the titrant.

2. The reaction should be rapid and quantitative. That is, the

equilibrium of the reaction should be far to the right so that a

sufficiently sharp change will occur at the end point to obtain the

desired accuracy.

3. There should be no side reactions; the reaction should be specific.

4. There should be a marked change in some property of the solution

when the reaction is complete. An indicator is generally added to

monitor this change.

5. The point at which an equivalent or stoichiometric amount of titrant

is added is called the equivalence point. The point at which the

reaction is observed to be complete is called the end point, that is,

when a change in some property of the solution is detected.

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Titration

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HOW DO WE MAKE STOICHIOMETRIC

CALCULATIONS?

A standard solution is prepared by dissolving an accurately weighed quantity of a

highly pure material called a primary standard and diluting to an accurately

known volume in a volumetric flask. Alternatively, if the material is not sufficiently

pure, a solution is prepared to give approximately the desired concentration, and

this is standardized by titrating a weighed quantity of a primary standard. A

solution standardized by titrating a primary standard is itself a secondary

standard.

A primary standard should fulfill these requirements:

1. It should be highly pure, with accurately known impurity.

2. It should be stable to drying temperatures, and indefinitely at room temperature.

3. It should be readily and relatively inexpensively available.

4. Although not essential, it should have a high formula weight.

5. If it is to be used in titration, it should possess the properties required for a

titration listed above. In particular, the equilibrium of the reaction should be far to

the right so that a sharp end point will be obtained. 49

Standard Solutions

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HOW DO WE MAKE STOICHIOMETRIC

CALCULATIONS?

1. Acid–Base. The end points of these titrations are easy to detect, either by

means of an indicator or by following the change in pH with a pH meter.

2. Precipitation. Titrant forms an insoluble product with the analyte. Again,

indicators can be used to detect the end point, or the potential of the

solution can be monitored electrically.

3. Complexometric. Titrant is a reagent that forms a water-soluble complex

with the analyte, a metal ion. The titrant is often a chelating agent like

Ethylenediaminetetraacetic acid (EDTA). Indicators can be used to form a

highly colored complex with the metal ion.

4. Reduction–Oxidation. These “redox” titrations involve the titration of an

oxidizing agent with a reducing agent, or vice versa. Appropriate indicators

for these titrations are available; various electrometric means to detect the

end point may also be used.

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Classification of Titration Methods

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VOLUMETRIC CALCULATIONS

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VOLUMETRIC CALCULATIONS

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VOLUMETRIC CALCULATIONS

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VOLUMETRIC CALCULATIONS

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VOLUMETRIC CALCULATIONS

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GRAVIMETRIC CALCULATIONS

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CHAPTER 6

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CHEMICAL EQUILIBRIUM

Learning Objectives

● The equilibrium constant

● Calculation of equilibrium concentrations

● The systematic approach to equilibrium calculations: mass balance and charge balance

equations

● Activity and activity coefficients

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Review of Equilibrium

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Review of Equilibrium

The “concentration” of a pure solid or liquid is unity.

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Equilibrium Constants for Dissociating or Combining

Species—Weak Electrolytes and Precipitates

Some species dissociate stepwise, and an equilibrium constant can be written for each dissociation step. A compound A2B, for example, may dissociate as follows:

When a substance dissolves in water, it will often partially or completely dissociate or ionize. Electrolytes that tend to dissociate only partially are called weak electrolytes, and those that tend to dissociate completely are strong electrolytes.

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When chemical species dissociate in a stepwise manner like this, the

successive equilibrium constants generally become progressively smaller. For

a diprotic acid (e.g., ), the dissociation of the second proton is

inhibited relative to the first (K2 < K1), because the negative charge on the

mono-anion makes it more difficult for the second proton to ionize.

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Equilibrium Constants for Dissociating or Combining

Species—Weak Electrolytes and Precipitates

If a reaction (like AB A + B) is written in the reverse, the same equilibria

apply, but the equilibrium constant is inverted. Thus, in the above example,

for A + B AB, Keq(reverse)= [AB]/([A][B]) = 1/Keq(forward). If Keq for the forward

reaction is 105, Kforward = 1/Kbackward then Keq for the reverse reaction is 10−5.

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Calculations Using Equilibrium Constants

** Repeat the calculations for K = 1x10-4

with and without approximation.

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Calculations Using Equilibrium Constants

The Common Ion Effect

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Calculations Using Equilibrium Constants

Equilibrium for complex systems Mass balance equations

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Calculations Using Equilibrium Constants

Equilibrium for complex systems Charge balance equations

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Calculations Using Equilibrium Constants

Equilibrium for complex systems Systematic Approach

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Calculations Using Equilibrium Constants

Equilibrium for complex systems Systematic Approach

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Calculations Using Equilibrium Constants

Equilibrium for complex systems Systematic Approach

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Activity and Activity Coefficients

The “effective concentration” of an ion is decreased by shielding it with other “inert” ions, and it represents the activity of the ion. This “effective concentration” of an ion in the presence of an electrolyte is called the activity of the ion. The activity of an ion ai is defined by: ai = Cifi , where Ci is the concentration of the ion i and fi is its activity coefficient. The activity coefficient varies with the total number of ions in the solution and with their charge, and it is a correction for interionic attraction. In dilute solution, less than 10−4M, the activity coefficient of a simple electrolyte is near unity, and activity is approximately equal to the concentration. Activity coefficient is a function of the total electrolyte concentration of the solution. The ionic strength is a measure of total electrolyte concentration and is defined by:

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Activity and Activity Coefficients

Debye and Huckel derived a theoretical expression for calculating activity coefficients, known as the Extended Debye–Huckel equation: A and B are constants; the values are, respectively, 0.51 and 0.33 for water at 25°C. ai is the ion size parameter, which is the effective diameter of the

hydrated ion in angstrom units, Å.

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Thermodynamic Equilibrium Constant

Equilibrium constants should more exactly be expressed in terms of activities rather than concentrations The numerical value of K°eq holds for all activities. Keq = K°eq at zero ionic

strength, but at appreciable ionic strengths, a value for Keq must be calculated for each ionic strength.

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