Pharmaceutical Analysis A
14 april 2020
Chapter 6: Chemical Equilibrium
Definition
Analytical Chemistry: Analytical chemistry is the science of obtaining, processing and
communicating information about the composite and structure of matter.
In other words it is the art and science of determining what matter is and how much of it exists.
Classification of analytical chemistry
1. According to method:
a. Classic wet chemistry: gravimetry, titrimetry
b. Instrumental or physicochemical methods
2. According to type of information:
a. Qualitative - Identity structure
b. Quantitative - amount of analyze in a sample
3. According to type of system or matter (application):
Pharmaceutical analysis, Forensic ad toxicological analysis, Food science, etc.
Pharmaceutical Analysis
Involves the analysis of medicinal drugs and compounds
1. Quality control of medicinal drugs and their dosage forms
2. Measurement of bioaccessibility (release of active substance from the drug)
3. Determination of bioavailability (distribution of active substance and its metabolites in the
body)
In the last case the sample is of biological origin (patient, animal) and the analysis thereof
is referred to as bioanalysis
THE ANALYTICAL PROCESS
The Analytical Process
Analyte: The compound to be analyzed in the chemical
analysis the analyte is present in the sample being sample measure- data
sampling
pretreatment ment analysis
analyzed.
There is always looked at the amount of analyte which
is available. validation
The analyte is the compound at which we are interested
in the concentration of the sample.
Analyte: the compound to be analysed in the chemical
The analytical process starts with taking a small sample from a largeranalysis;
amounttheofanalyte
material. Thatin the sample
is present
sample is usually subjected to some kind of sample pretreatment. You need
being to clean up the
analysed
sample if there are a lot of products in it. This is needed so you can also measure the specific 25
product you are interested in. With no interference of other compounds. You can take the results
and analyze these. Than you know how much of the compound -> analyte you are interested in is
present in the sample you took.
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,Classic, wet-chemical quantitative methods
Gravimetry:
- The analyte is precipitated (neergeslagen) by addition of a reagent to form an insoluble solid
- The amount of predicate produced is rinsed, dried and weighed and the original concentration
of analyte is calculated
Example: Ag + + Cl − ⇄ AgCl(s) -> used for Cl- analysis
You add too much Ag ions to know for sure that all the chloride ions have reacted. You can take
the silver chloride and you can rinse away the silver and than you determine the amount of
chloride in the silver chloride.
- Gravimetry is an exceptionally accurate analysis method but is very laborious Classic,
to carry wet-chemical
out quantitativ
- It is now mostly used to prepare standards for calibration of analytical apparatus.
methods (2)
Titrimetry:
Titrimetry:
There is a solution containing an analyte of interest but with an unknown
concentration. In this experience we want to find out the concentration of the analyte.
Determination of the unknown amount of analyte A, in a solution by measuring the
consumption of a reagent T, that reacts with A
A + T → AT
A: Analyte A (in the sample, S) http://img.sparknotes.com/figures/3/3a5994498f24d59f5d5d762b40844
T: The reagent reacted with A, The reagent is contained in a solution called the “titrant”
T -> Concentration is known A -> Concentration is unknown
This analysis method makes use of a chemical reaction
- Analyte A is reacted / converted by addition of small, precisely measured volumes of titrant
containing a known concentration of T
- Equivalence point: The amount of reagent, T (and thus titrant), added is exactly the same as the
amount required to convert all of analyte A to product AT
- So the amount of T added is the same as the amount of A in the sample.
Chemical Reaction —> Chemical equilibrium
A + T → AT
- Choose a reaction in which all the T added each time is completely reacted with A to produce
AT
Shortly after each addition of T : Equilibrium
A + T ⇄ AT
When a reaction has reached equilibrium the forward and reverse rates of reaction are equal.
In other word: The concentrations of A, T and AT remain the same.
- The concentration of T is very, very small
At the equivalence point: Equilibrium
- The concentration of both A and T are very small. All the A has formed reacted with T and there
is formed AT. There is still a small concentration of A and T
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, Laws of chemical equilibrium
1. Law of Mass Action (Guldberg and Waage)
2. La Chatelier’s Principle OR The equilibrium law (Le Chatelier & van’t Hoff)
Law of Mass Action:
At a given temperature, a chemical system reaches a state in which a particular ratio of reactant
and product concentration has a constant value
The Equilibrium Constant, K:
K = [C ]c[D]d
a A + bB ⇄ cC + d D —>
[A]a[B]b
A, B, C, D: Chemical compounds
a, b, c, d: Indicate how many molecules of given compound take part in the reaction (these
lowercase superscript letters are called “stoichiometry coefficients”)
[A], etc.: These are concentrations of the reacting compounds (mol/L for compounds
dissolved in solution)
- If a reacting compound is a gas, concentration will be gives as PA instead of [A] in
units of pressure (for example, in bar)
[A], [B], [C], [D] in the equation for K:
- each of these quantities is actually expressed as the ratio of the concentration of the species to
its concentration in its standard state.
- For example: [A] in its standard state, [A]stan =1 M
- Therefore: [A] is [A]/(1M), [B] is [B]/(1M), etc.
- For a gas, D: PD is PD/(1 bar)
- Concentrations of pure solids and pure liquids: [A]/[A]stan = 1
- Concentrations of solvents (when dissolved analyte concentrations are low): [A]/[A]stan = 1
- M -> mol/liters
- Stan = Standard condition
K is dimensionless - in other words, K has no units (e.g. no moles, grams, liters, etc.)
When K > 1, the numerator is greater than the denominator. The equilibrium lies to the right. Th
reaction is favored Working with Equilibrium Constants, K
Stoichiometry: Ratios of substances participating in a chemical reaction
(Stoicheion = element, Metron = size) Example 1: Reversing a reaction
Working with Equilibrium Constants, K [H ][ A ]
HA(aq) H+(aq) + A-(aq) K1
Example 1: Reversing a reaction [HA]
Working withIfEquilibrium Constants,
we reverse the reaction K
than we change the equilibrium Reverse the reaction:
constant as well.
xample 2: Adding reactions ' [HA] 1
H+(aq) + A-(aq) HA(aq) K1
[H ][ A -] K1
NO2(g) + NO2(g) NO3(g) + NO(g) K1
NO3(g) + CO(g) NO2(g) + CO2(g) K2
Example 2: Adding reactions
NO2(g) + CO(g) NO(g) + CO2(g) K3 If a reaction consist of two sub reactions and are coming together 36
than this changes also the equilibrium constant.
[NO3 ][NO] [NO 2 ][CO 2 ] [NO][CO 2 ]
K KK
3 1 2
[NO 2 ][NO 2 ] [NO3 ][CO] [NO 2 ][CO]
37
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, The equilibrium Law (or Le Châterlier’s Principle): Le Châtelier and van ’t Hoff (1885)
When a system at the equilibrium is subjected to a change that disturbs the system, the system
will read just itself to partly counteract the effect of the applied change so as to proceed back to
equilibrium.
The Equilibrium Law
Example: effect of changes in concentration of a reactant or product
(reaction takes place in water)
BrO3- + 2Cr3+ + 4H2O ⇌ Br- + Cr2O72- + 8H+
Bromate Chromium(3) Bromide Dichromate
[Br −][Cr 2O 72][H+]8
K= = 1 x 1011 at 25 Cº
[BrO3−][Cr 3]2
- Add dichromate: What happens?
- At constant temperature, T: K remains constant
- The reaction system readjusts to THE LEFT ( reactant and product concentration shift) until the
system’s K value is reestablished
The Equilibrium Law
System in equilibrium
Reactant ⇄ Product
Remove product, -> Reaction proceeds to the right…
… Until the equilibrium is re-established
- Add reactant -> Reaction proceeds to the right
- Add Product -> Reaction proceeds to the left
- Take product away -> Reaction proceeds to the right
- Take reactant away -> Reaction proceeds to the left
BrO3- + 2Cr3+ + 4H2O ⇌ Br- + Cr2O72- + 8H+
Bromate Chromium(3) Bromide Dichromate
[Br −][Cr 2O 72][H+]8
K= = 1 x 1011 at 25 Cº
[BrO3−][Cr 3]2
In one equilibrium condition the following concentrations were found:
[H+] = 4.0 M [Cr2O72-] = 0.10 M [Cr3+] = 0.003 M
[Br-] = 1.0 M [BrO3-] = 0.043 M
Say [Cr2O72-] is increased form 0.10 M to 0.20 M
In which direction does the system readjust itself?
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