LECTURE № 1
Theme: Course introduction and
importance of Pharmaceutical Chemistry
for pharmaceutical analysis. Introduction
about Pharmacopoeia and methods of
drug analysis.
Inorganic drugs from group of
halogenides of alkaline metals.
Associate prof. Mosula L.M.
The plan
1. A subject and the contents of pharmaceutical chemistry, its
interrelation with chemical, medical and biologic and
pharmaceutical disciplines.
2. The State Pharmacopoeia of Ukraine (SPU), the International
(Ph. Int.), Europian (Ph. Eur.) and British Pharmacopoeias (BP),
and other analytical normative documentation (AND), which
regulates high quality of pharmaceutical preparations.
4. Classification of drugs.
5. Inorganic drugs from group of halogenides of alkaline metals:
obtaining, properties (appearance and solubility), identification,
tests, assay, storage, action and use of preparations of:
Fluorine (sodium fluoride);
Chlorine (sodium and potassium chlorides);
Bromine (sodium and potassium bromides);
Iodine (sodium and potassium iodides).
Pharmaceutical chemistry is a highly interdisciplinary science
combining organic chemistry with biochemistry, inorganic chemistry, analytical
chemistry, pharmacology, pharmacognosy, molecular biology and physical
chemistry.
Pharmaceutical chemistry is the chemistry of drugs and
pharmaceutical products.
The aim of pharmaceutical chemistry is the discovery and
development of new therapeutic agents.
The mission of the Pharmaceutical Chemistry course is to
introduce the structure, properties, and analysis (both qualitative and
quantitative) of pharmaceutical agents as well as the fundamental techniques
used for near patient testing in clinical laboratories to the students. Topics
include some of the basic concepts in pharmaceutical chemistry as well as
methods of pharmaceutical analysis such as 1) the drug synthesis, 2) review of
organic functional groups found in drug molecules as well as cations and anions
of the inorganic drugs, 3) physicochemical properties related to drug action, 4)
physicochemical and chemical analysis of drugs, 5) methods of identification of
pharmaceutical agents, 6) the storage conditions and use of drugs.
Pharmaceutical Chemistry is a multifaceted discipline that
encompasses synthetic organic chemistry, inorganic, analytical,
physical, colloidal, biological chemistry and some disciplines of
medical and biological profile: biology, normal and pathological
physiology, microbiology. The pharmaceutical chemistry is closely
connected with other profile disciplines: pharmacognosy, technology
of medicines, the organisation and pharmacy economy,
pharmacotherapy.
Pharmaceutical chemistry is a discipline at the intersection of
chemistry and pharmacology involved with designing, synthesizing
and developing pharmaceutical drugs.
Compounds used as medicines are overwhelmingly organic
compounds including small organic molecules and biopolymers.
However, inorganic compounds and metal-containing compounds
have been found to be useful as drugs.
Drugs are prepared from Pharmaceutical Substances.
Pharmaceutical Substances is designed to be a complete
reference guide to every pharmaceutical compound of
significance. It provides a compendium of some 2400 active
pharmaceutical ingredients (API's) of interest to the chemical and
pharmaceutical industries. Pharmaceutical Substances is an
invaluable resource for anybody involved in the design, discovery,
development, and evaluation of drugs.
Pharmacopoeia in its modern technical sense, is a book containing
directions for the identification of samples and the preparation of compound
medicines, and published by the authority of a government or a medical or
pharmaceutical society.
The word derives from Ancient Greek φαρμακοποιεια (pharmakopoieia),
from φαρμακο- (pharmako-) 'drug', followed by the verb-stem ποιε- (poie-)
'make' and finally the abstract noun ending -ια (-ia). These three elements
together can be rendered as 'drug-mak-ing'.
The aim of the International Pharmacopoeia (Ph. Int.), which is issued
by the World Health Organization as a recommendation, is to achieve a wide
global uniformity of quality specifications for selected pharmaceutical products,
excipients, and dosage forms. The information published in the International
Pharmacopoeia is collated via a consultative procedure and is based on
international experience, the monographs being established in an independent
manner. Priority is given to medicines that are widely used throughout the
world. High priority is accorded to medicines that are important to WHO health
programs, and which may not appear in any other pharmacopoeias.
The European Pharmacopoeia (Ph. Eur.) of the Council of Europe is a
pharmacopoeia, listing a wide range of active substances and excipients used to
prepare pharmaceutical products in Europe[citation needed]. The 2005 edition
includes 1800 specific and general monographs, including various chemical
substances, antibiotics, biological substances. The European Pharmacopoeia is
developed by the European Directorate for the Quality of Medicines (EDQM) and
is a part of the Council of Europe, Strasbourg, France. It has been created by the
Convention on the elaboration of a European Pharmacopoeia from 1964.
The British Pharmacopoeia (BP) is an annual published collection of quality
standards for UK medicinal substances. It is used by individuals and
organizations involved in pharmaceutical research, development, manufacture
and testing. Pharmacopoeial standards are publicly available and legally
enforceable standards of quality for medicinal products and their constituents.
The Pharmacopoeia is an important statutory component in the control of
medicines which complements and assists the licensing and inspection processes
of the Medicines and Healthcare products Regulatory Agency (MHRA) of the
United Kingdom. Pharmacopoeial standards are compliance requirements; that
is, they provide the means for an independent judgment as to the overall quality
of an article and apply throughout the shelf-life of a product. Inclusion of a
substance in a pharmacopoeia does not indicate that it is either safe or effective
for the treatment of any disease.
The State Pharmacopoeia of Ukraine (SPU) is a legal
document which contains the general requirements to
pharmaceutical preparations, monographies (pharmaceutical
articles) as well as techniques of quality assurance of medical
products. The first edition of SPU was published in 2001. It has
legislative character and its requirements are obligatory for all
enterprises and establishments, independently on a form of property
which develop, keep, supervise, realize and apply medical products.
Quality assurance of drugs in Ukraine at the state level is
carried out by Ministry of Public Health. It supervises the service of
medical products and products of medical appointment, the State
Enterprise „Scientific and Expert Pharmacopoeial Centre”, the State
Pharmacological Centre, the State Drugs inspection (its structure
includes the Central laboratory of quality assurance of medical
products), territorial inspections of quality assurance of medical
products.
Impurities are substances inside a confined amount of liquid,
gas, or solid, which differ from the chemical composition of the
material or compound.
Impurities are either naturally occurring or added during
synthesis of a chemical or commercial product. During
production, impurities may be purposely, accidentally,
inevitably, or incidentally added into the substance.
The level of impurities in a material are generally defined in
relative terms. Standards have been established by various
organizations that attempt to define the permitted levels of
various impurities in a manufactured product. Strictly speaking,
then, a material's level of purity can only be stated as being more
or less pure than some other material.
Destructive impurities
Impurities can be destructive when they obstruct the working nature of
the material. Examples include ash and debris in metals and leaf pieces
in blank white papers. The removal of impurities is usually done
chemically. For example, in the manufacturing of iron, calcium carbonate
is added to the blast furnace to remove silicon dioxide from the iron ore.
Zone refining is an economically important method for the purification
of semiconductors.
However, some kinds of impurities can be removed by physical means. A
mixture of water and salt can be separated by distillation, with water as
the distillate and salt as the solid residue. Impurities are usually
physically removed from liquids and gases. Removal of sand particles
from metal ore is one example with solids.
No matter what method is used, it is usually impossible to separate an
impurity completely from a material. What technicians can do is to
increase the purity of a material to as near 100% as possible or
economically feasible.
There are two types of impurities: general and specific.
The sources of general impurities are equipment, solvents, auxiliary
materials, and of specific ones – by-products, semiproducts of synthesis of
substances of medicinal forms and compounds which are formed in medical
products at their wrong storage.
The State Pharmacopoeia of Ukraine, other Analytical Normative
Documentation (AND) on the basis of experimental researches regulate
specific impurities and their quantity for each preparation.
For revealing the impurities in the medical products and their approximate
quantitative estimation use standard solutions (standards).
Standard solution is a chemical term which describes a solution of
known concentration of testing impurity. The concentration of the solution
is normally expressed in unit of ppm (parts-per-million, ppm = 10–6) (One
part per million (ppm) denotes one part per 1,000,000 parts, one part in 106,
and a value of 1 × 10–6.). For standards (standard solutions) preparation
use chemically pure initial substances (mother substances).
Presence of impurities defines by means of such methods: nephelometry
and colorimetry.
At the revealing same impurities use instrumental methods of analysis (atomic
absorption spectroscopy, spectrophotometry, chromatography, etc.).
The proposed program will you prepare to fully and
confidently participate in health and biomedical careers.
Pharmaceutical companies need employees with strong
skills in modern chemical techniques as well as a good
understanding of biomedical issues such as drug action, drug design
and drug development. Students are increasingly careeroriented and
are motivated by early exposure to applications of their studies.
Pharmacists are health professionals who practice the
science of pharmacy. It is very important propfession.
Browse: British Pharmacopoeia 2009
SPU, add. 1
General Notices
(Ph Eur monograph 0193)
58.44
Sodium Chloride
NaCl
DEFINITION
Content
99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals or white or almost
white
pearls.
Solubility
Freely soluble in water, practically insoluble in anhydrous ethanol.
OBTAINING:
1. From water of lakes and the seas by evaporation.
2. Clarification of technical mineral salt NaCl from impurity, which
carry out consistently. Addition of a solution barium chloride
ВаCl2 is precipitates by sulphates and phosphates:
SO42– + Ba2+  BaSO4
HPO42– + Ba2+  BaHPO4
Precipitate filter off, and to filtrate add excess of Na2CO3 for
precipitation of impurities of Mg, Ca, Ba salts.
Mg2+ + CO32–  MgCO3
Ca2+ + CO32–  CaCO3
Ba2+ + CO32–  BaCO3
For deleting of exess of Na2CO3 to filtrate add HCl:
Na2CO3 + 2HCl = 2NaCl + H2O + CO2
IDENTIFICATION
A. It gives the reactions of chlorides (2.3.1).
Chlorides:
A. (BrPh, SPU, add. 1). Reaction with solution of
AgNO3 in the nitric-acid medium.
Dissolve in 2 ml of water R a quantity of the substance to be examined
equivalent to about 2 mg of chloride (Cl–) or use 2 ml of the prescribed solution.
Acidify with dilute nitric acid R and add 0.4 ml of silver nitrate solution R1.
Shake and allow to stand. A curdled, white precipitate is formed. Centrifuge and
wash the precipitate with three quantities, each of 1 ml, of water R. Carry out this
operation rapidly in subdued light, disregarding the fact that the supernatant
solution may not become perfectly clear. Suspend the precipitate in 2 ml of water
R and add 1.5 ml of ammonia R. The precipitate dissolves easily with the
possible exception of a few large particles which dissolve slowly.
NaCl + AgNO3 → AgCl↓ + NaNO3;
Cl– + Ag+ → AgCl↓
curdled, white precipitate
AgCl↓ + 2NH4OH → [Ag(NH3)2]Cl + 2H2O
B. (BrPh, SPU, add. 1). Reaction with oxidizers in
the acid medium with the next identification of toxic gas –
Cl2.
Introduce into a test-tube a quantity of the substance to be examined equivalent to
about 15 mg of chloride (Cl–) or the prescribed quantity. Add 0.2 g of potassium
dichromate R and 1 ml of sulphuric acid R. Place a filter-paper strip impregnated with
0.1 ml of diphenylcarbazide solution R over the opening of the test-tube. The paper
turns violet-red. The impregnated paper must not come into contact with the potassium
dichromate.
6NaCl + K2Cr2O7 + 7H2SO4 = 3Cl2 + Cr2(SO4)3 + K2SO4 + 3Na2SO4 + 7H2O
Cr2O72– + 14H+ + 6е  2Cr3+ + 7Н2О
2Cl– – 2е  Cl2
NH
NH
C H
C H
N
C H
N
6
O
C
NH
NH
5
+ CL2
C 6H5 -2 HCl
diphenylcarbazide
(colourless)
N
O
N
6
5
+ CL2
C
NH
NH
C 6H5 -2 HCl
diphenylcarbadiazone
(orange-yellow)
6
O
5
C
N
N
C 6H5
diphenylcarbazone
(violet-red)
B. It gives the reactions of sodium (2.3.1).
Sodium and Sodium Salts:
A. (BrPh, SPU, add. 1). Reaction with potassium pyroantimonate
solution.
Dissolve 0.1 g of the substance to be examined in 2 ml of water R or use 2 ml of the
prescribed solution. Add 2 ml of a 150 g/l solution of potassium carbonate R and
heat to boiling. No precipitate is formed. Add 4 ml of potassium pyroantimonate
solution R and heat to boiling. Allow to cool in iced water and if necessary rub the
inside of the test-tube with a glass rod. A dense white precipitate is formed.
NaCl + K[Sb(OH)6] → Na[Sb(OH)6]↓ + KCl
Na+ + [Sb(OH)6]– Na[Sb(OH)6]
dense white precipitate
B. Reaction with methoxyphenylacetic reagent.
Dissolve a quantity of the substance to be examined equivalent to about 2 mg of sodium
(Na+) in 0.5 ml of water R or use 0.5 ml of the prescribed solution. Add 1.5 ml of
methoxyphenylacetic reagent R (it is solution of methoxyphenylacetic acid in the
tetramethylammonium hydroxide solution and ethanol) and cool in ice-water for 30
min. A voluminous, white, crystalline precipitate is formed. Place in water at 20 °C
and stir for 5 min. The precipitate does not disappear. Add 1 ml of dilute ammonia
R1. The precipitate dissolves completely. Add 1 ml of ammonium carbonate solution
R. No precipitate is formed.
O
H
C
+
C
OCH3
O
CH3
H
C
NOH
4
OCH3
OH
O
H
C
OCH3
O
ON(CH3)4
O
+
C
C
Na +
H
C
C
OCH3
ONa
white, crystalline
precipitate
Other reaction:
SPU, N. Pyrochemical reaction. Sodium salt, wetted with hydrochloric acid
and brought in a colourless flame, paints its in yellow colour:
Na+ + hν → *Na+ → Na+ + hν1.
TESTS
If the substance is in the form of pearls crush before use.
Solution S
Dissolve 20.0 g in carbon dioxide-free water R prepared from distilled water R and
dilute to
100.0 ml with the same solvent.
Ferrocyanides - inadmissible impurity.
Dissolve 2.0 g in 6 ml of water R. Add 0.5 ml of a mixture of 5 ml of a 10 g/l
solution of ferric ammonium sulphate R in a 2.5 g/l solution of sulphuric acid R and
95 ml of a 10 g/l solution of ferrous sulphate R. No blue colour develops within
10 min.
4Fe3+ + 3[Fe(CN)6]4–  Fe4[Fe(CN)6]3
3Fe2+ + 2[Fe(CN)6]3–  Fe3[Fe(CN)6]2
Iodides - inadmissible impurity.
Moisten 5 g by the dropwise addition of a freshly prepared mixture of 0.15 ml of
sodium nitrite solution R, 2 ml of 0.5 M sulphuric acid , 25 ml of iodide-free starch
solution R and 25 ml of water R. After 5 min, examine in daylight. The mixture
shows no blue colour.
2I– + 2NO2– + 4H+  I2 + 2NO + 2H2O
Barium - inadmissible impurity.
To 5 ml of solution S add 5 ml of distilled water R and 2 ml of dilute sulphuric acid
R. After 2h, any opalescence in the solution is not more intense than that in a
mixture of 5 ml of solution S and 7 ml of distilled water R.
Ва2+ + SO42–  ВаSO4 
ASSAY
(BrPh, SPU, add. 1). Argentometry, direct titration
with potentiometric fixation of end-point.
Dissolve 50.0 mg in water R and dilute to 50 ml with the same
solvent. Titrate with 0.1 M silver nitrate determining the end-point
potentiometrically (2.2.20).
1 ml of 0.1 M silver nitrate is equivalent to 5.844 mg of NaCl.
NaCl + AgNO3 = AgCl↓ + NaNO3
Еm(NaCl) = M. m.
Other methods:
1.SPU, add. 1. Thiocyanatometry.
2. SP X. Argentometry, direct titration (Morh method).
Indicator – K2CrO4.
3. Argentometry, back titration (Volhard method) (see thiocyanatometry). To
investigated solution add double excess of standart solution of AgNO3.
NaCl + AgNO3 = AgCl + NaNO3
AgNO3 + NH4SCN = AgSCN + NH4NO3
3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 + 2(NH4)2SO4
Еm(NaCl) = M. м.
Argentometry, direct titration (Fajance method).
Indicator – fluoresceine.
NaCl + AgNO3 = AgCl  + NaNO3
Еm(NaCl) = M. м.
5. Mercurymetry, direct titration.
Indicator – diphenylcarbazone.
To titrate until changing of colouring solution from yellow-red to dark blue colour.
2NaCl + Нg(NO3)2 = НgCl2 + 2NaNO3
Еm(NaCl) = M. м.
In the equivalence point excess drop of titrant Нg(NO3)2 interaction with indicator of
diphenylcarbazone and formation of dark blue complex.
N
2O
N
C
NH
NH
N
C6H5
+
C6H5
Hg(NO3)2
O
C6H5
C6H5
N
N
N
N
N
NH
C6H5
C6H5
C
Hg
C
NH
O + 2 HNO3
Leybeling
— where applicable, that the substance is suitable for use in the manufacture of
parenteral dosage forms;
— where applicable, that the substance is suitable for use in the manufacture of
peritoneal dialysis solutions, haemodialysis solutions or haemofiltration solutions.
Action and use
Used in treatment of electrolyte deficiency.
Plasma substitute.
Ions Na + are basic extracellular Ions. It is the basic component of all salt
solutions, which are applied as plasma substitutes.
Isotonic (0,9 %) a solution of sodium chloride (Solutіo Natrіі chlorіdі іsotonіca pro
іnjectіonіbus) apply hypodermically, intravenously (more often drop method) and in clyster
as antitoxic means and at organism dehydration, at bleedings, a shock (sometimes - to 3 L).
Introduction of great volumes of this solution can lead chloride acidisis, hyperhydrations,
strengthening of conclusion of Potassium from an organism.
Preparations
Compound Glucose, Sodium Chloride and Sodium Citrate Oral Solution
Oral Rehydration Salts
Potassium Chloride and Sodium Chloride Intravenous Infusion
Potassium Chloride, Sodium Chloride and Glucose Intravenous Infusion
Sodium Chloride Eye Drops
Sodium Chloride Eye Lotion
Sodium Chloride Intravenous Infusion
Sodium Chloride and Glucose Intravenous Infusion
Sodium Chloride Irrigation Solution
Compound Sodium Chloride Mouthwash
Sodium Chloride Oral Solution
Sodium Chloride Solution
Sodium Chloride Tablets
Browse: British Pharmacopoeia 2009
SPU, add. 1
Kalіі chlorіdum
Potassium chloride
KCl
74.6
DEFINITION
Content
99.0 per cent to 100.5 per cent of KCl (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals.
Solubility
Freely soluble in water, practically insoluble in anhydrous ethanol.
OBTAINING:
1.Clarification of Potassium natural salt from impurities (analogical to
NaCl).
Identification
A. It gives the reactions of chlorides (2.3.1).
Chlorides
A. (BrPh, SPU, add. 1) Reaction with solution of AgNO3 in
the nitricacid medium.
Dissolve in 2 ml of water R a quantity of the substance to be examined
equivalent to about 2 mg of chloride (Cl–) or use 2 ml of the prescribed
solution. Acidify with dilute nitric acid R and add 0.4 ml of silver nitrate
solution R1. Shake and allow to stand. A curdled, white precipitate is formed.
Centrifuge and wash the precipitate with three quantities, each of 1 ml, of
water R. Carry out this operation rapidly in subdued light, disregarding the
fact that the supernatant solution may not become perfectly clear. Suspend
the precipitate in 2 ml of water R and add 1.5 ml of ammonia R. The
precipitate dissolves easily with the possible exception of a few large
particles which dissolve slowly.
KCl + AgNO3 → AgCl↓ + KNO3;
Cl– + Ag+ → AgCl↓
AgCl↓ + 2NH4OH → [Ag(NH3)2]Cl + 2H2O
B. SPU. Reaction with oxidizers in the acid medium
with the next identification of toxic gas – Cl2.
Introduce into a test-tube a quantity of the substance to be examined equivalent
to about 15 mg of chloride (Cl–) or the prescribed quantity. Add 0.2 g of
potassium dichromate R and 1 ml of sulphuric acid R. Place a filter-paper strip
impregnated with 0.1 ml of diphenylcarbazide solution R over the opening of
the test-tube. The paper turns violet-red. The impregnated paper must not come
into contact with the potassium dichromate.
6KCl + K2Cr2O7 + 7H2SO4 = 3Cl2 + Cr2(SO4)3
+ 4K2SO4 + 7H2O
Cr2O72– + 14H+ + 6е  2Cr3+ + 7Н2О
2Cl– – 2е  Cl2
NH
O
NH
C
NH
NH
C6H5 + CL
2
C6H5 -2 HCl
N
O
diphenylcarbazide
(colourless)
N
C6H5
+ CL2
C
NH
NH
O
C6H5 -2 HCl
diphenylcarbadiazone
(orange-yellow)
N
N
C6H5
N
N
C6H5
C
diphenylcarbazone
(violet-red)
B. Solution S (see Tests) gives the reactions of
potassium (2.3.1).
Potassium and Potassium Salts:
A. (BrPh). Reaction with tartaric acid.
Dissolve 0.1 g of the substance to be examined in 2 ml of water R or use 2 ml of
the prescribed solution. Add 1 ml of sodium carbonate solution R and heat. No
precipitate is formed. Add to the hot solution 0.05 ml of sodium sulphide solution
R. No precipitate is formed. Cool in iced water and add 2 ml of a 150 g/l solution
of tartaric acid R. Allow to stand. A white crystalline precipitate is formed.
O
O
C
+
K
HO
C
CH
OH
HO
CH
OH
+
+
HO
CH
HO
CH
OH
C
+
H .
OK
C
O
O
white crystalline precipitate
B. (BrPh). Reaction with sodium cobaltinitrite.
Dissolve about 40 mg of the substance to be examined in 1 ml of water R or use
1 ml of the prescribed solution. Add 1 ml of dilute acetic acid R and 1 ml of a
freshly prepared 100 g/l solution of sodium cobaltinitrite R. A yellow or orangeyellow precipitate is formed immediately.
2KBr + Na3[Co(NO2)6] → K2Na[Co(NO2)6]↓ +
2NaBr.
+
+
2К + Na + [Co(NO2)6]3– → K2Na[Co(NO2)6]↓
orange-yellow precipitate
Other reaction:
SPU, N. Pyrochemical reaction. Potassium Salt, wetted with hydrochloric acid
and brought in a colourless flame, paints its in violet colour:
К+ + hν → *К+ → К+ + hν1.
TESTS
Solution S
Dissolve 10.0 g in carbon dioxide-free water R prepared from distilled water R
and dilute to 100 ml with the same solvent.
Iodides–inadmissible impurity.
Moisten 5 g by the dropwise addition of a freshly prepared mixture of 0.15 ml of
sodium nitrite solution R, 2 ml of 0.5 M sulphuric acid , 25 ml of iodide-free
starch solution R and 25 ml of water R. After 5 min, examine in daylight. The
substance shows no blue colour.
2I– + 2NO2– + 4H+  I2 + 2NO + 2H2O
Barium–inadmissible impurity.
To 5 ml of solution S add 5 ml of distilled water R and 1 ml of dilute sulphuric
acid R. After 15 min, any opalescence in the solution is not more intense
than that in a mixture of 5 ml of solution S and 6 ml of distilled water R.
Ва2+ + SO42–  ВаSO4 
Sodium–inadmissible impurity.
Maximum 0.10 per cent, if intended for use in the manufacture of
parenteral preparations or haemodialysis solutions. Atomic emission
spectrometry (2.2.22, Method I).
ASSAY
(BrPh, SPU, add. 1). Argentometry, back titration
(thiocyanatometry).
Dissolve 1.300 g in water R and dilute to 100.0 ml with the same solvent. To 10.0
ml of the solution add 50 ml of water R, 5 ml of dilute nitric acid R, 25.0 ml of 0.1
M silver nitrate and 2 ml of dibutyl phthalate R. Shake. Titrate with 0.1 M
ammonium thiocyanate, using 2 ml of ferric ammonium sulphate solution R2 as
indicator and shaking vigorously towards the endpoint.
1 ml of 0.1 M silver nitrate is equivalent to 7.46 mg of KCl.
КCl + AgNO3 = AgCl + КNO3
Еm(КCl) = M. м.
AgNO3 + NH4SCN = AgSCN + NH4NO3
3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 +
2(NH4)2SO4
Other methods:
1. Argentometry (Моrh method) (see NaCl)
Еm(КCl) = M. m.
3. Argentometry (Fajance method) (see NaCl)
Еm(КCl) = M. m.
4. Mercurymetry (see NaCl)
Еm(КCl) = M. m.
LABELLING
The label states:э
э— where applicable, that the substance is suitable for use in the manufacture of parenteral
preparations;
э— where applicable, that the substance is suitable for use in the manufacture of
haemodialysis solutions.
Ph Eur
Action and use
Used in prevention and treatment of potassium deficiency and electrolyte imbalance.
A source of ions of Potassium, antiarrhytmic agent.
Release forms: a powder, tablets - 0,5 g and 1 g, 4 % a solution for injections; 10 %
a solution for oral using.
Preparations
Bumetanide and Prolonged-release Potassium Tablets
Oral Rehydration Salts
Sterile Potassium Chloride Concentrate
Potassium Chloride and Glucose Intravenous Infusion
Potassium Chloride and Sodium Chloride Intravenous Infusion
Potassium Chloride, Sodium Chloride and Glucose Intravenous Infusion
Potassium Chloride Oral Solution
Prolonged-release Potassium Chloride Tablets
Ph Eur
Browse: British Pharmacopoeia 2009
SPU, add. 1
General Notices
(Ph Eur monograph 0190)
102.9
Sodium Bromide
NaBr
DEFINITION
Content
98.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, granular powder or small, colourless, transparent or opaque
crystals,
slightly hygroscopic.
Solubility
Freely soluble in water, soluble in alcohol.
Obtaining:
Processing of iron scraps by means of bromine:
3Fe + 4Br2 = Fe3Br8
Received of solution of iron (II) bromide and iron (III) bromides to heat with solution
of sodium carbonate Na2CO3 or potassium carbonate К2CO3:
4H2O + Fe3Br8 + 4Na2CO3 = Fe(OH)2 +
2Fe(OH)3 + 8NaBr + 4CO2
4H2O + Fe3Br8 + 4К2CO3 = Fe(OH)2 +
2Fe(OH)3 + 8КBr + 4CO2
IDENTIFICATION
A. It gives reaction (a) of bromides (2.3.1).
Bromides:
A. (BrPh). Reaction with silver nitrate in the nitric
acid medium. Dissolve in 2 ml of water R a quantity of the substance to
be examined equivalent to about 3 mg of bromide (Br–) or use 2 ml of the
prescribed solution. Acidify with dilute nitric acid R and add 0.4 ml of silver
nitrate solution R1. Shake and allow to stand. A curdled, pale yellow
precipitate is formed. Centrifuge and wash the precipitate with three
quantities, each of 1 ml, of water R. Carry out this operation rapidly in subdued
light disregarding the fact that the supernatant solution may not become
perfectly clear. Suspend the precipitate obtained in 2 ml of water R and add 1.5
ml of ammonia R. The precipitate dissolves with difficulty.
KBr + AgNO3 → AgBr↓ + KNO3;
+
–
Ag + Br = AgBr↓
AgBr↓ + 2NH4OH → [Ag(NH3)2]Br + 2H2O
Other reactions:
B. (BrPh). Introduce into a small test-tube a quantity of the substance
to be examined equivalent to about 5 mg of bromide (Br–) or the prescribed
quantity. Add 0.25 ml of water R, about 75 mg of lead dioxide R, 0.25 ml of
acetic acid R and shake gently. Dry the inside of the upper part of the testtube with a piece of filter paper and allow to stand for 5 min. Prepare a strip
of suitable filter paper of appropriate size. Impregnate it by capillarity, by
dipping the tip in a drop of decolorised fuchsin solution R and introduce the
impregnated part immediately into the tube. Starting from the tip, a violet
colour appears within 10 s that is clearly distinguishable from the red colour
of fuchsin, which may be visible on a small area at the top of the
impregnated part of the paper strip.
2NaBr + PbО2 + 4CH3COOH = Br2 + Pb(CH3COO)2 + 2CH3COONa + 2H2O
PbО2 + 4H+ + 2е  Pb2+ + 2Н2О
2Br– – 2е  Br2
Bromine Br2, which allocated, react with decolorised fuchsin solution R in the
indicator paper and,as oxidizing agent, reduce again structure of fuchsin:
+
H2N
H2N
NH
C
HCl
Cl
NH2
NHSO3H
C
SO3H
Na2SO3
NH2
B. Solution S (see Tests) gives the reactions of sodium
(2.3.1).
Sodium and Sodium Salts:
A. (BrPh, SPU). Reaction with potassium pyroantimonate
solution.
B. (BrPh, SPU). Reaction with methoxyphenylacetic reagent.
Other reaction:
SPU, N. Pyrochemical reaction.
TESTS
Solution S
Dissolve 10.0 g in carbon dioxide-free water R prepared from distilled water R and
dilute to 100 ml with the same solvent.
Bromates –inadmissible impurity.
To 10 ml of solution S add 1 ml of starch solution R, 0.1 ml of a 100 g/l solution of potassium
iodide R and 0.25 ml of 0.5 M sulphuric acid and allow to stand protected from light for 5 min.
No blue or violet colour develops.
5Br– + BrО3– + 6H+ = 3Br2 + 3H2O
Br2 + KI = 2KBr + I2
Iodides –inadmissible impurity.
To 5 ml of solution S add 0.15 ml of ferric chloride solution R1 and 2 ml of methylene chlorideR.
Shake and allow to separate. The lower layer is colourless (2.2.2, Method I).
This reaction is not presents: 2I– + 2Fe3+  I2 + 2Fe2+
ASSAY
(BrPh, and SPU, add. 1). Thiocyanatometry.
Dissolve 2.000 g in water R and dilute to 100.0 ml with the same solvent. To 10.0 ml
of the solution add 50 ml of water R, 5 ml of dilute nitric acid R, 25.0 ml of 0.1 M
silver nitrate and 2ml of dibutyl phthalate R. Shake. Titrate with 0.1 M ammonium
thiocyanate, using 2 ml of ferric ammonium sulphate solution R2 as indicator and
shaking vigorously towards the endpoint.
1 ml of 0.1 M silver nitrate is equivalent to 10.29 mg of NaBr.
NaBr + AgNO3 = AgBr + NaNO3
AgNO3 + NH4SCN = AgSCN + NH4NO3
3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 + 2(NH4)2SO4
Еm(NaBr) = M. m.
Calculate the percentage content of NaBr from the expression:
A – 2.902 b
a=percentage content of NaBr and NaCl obtained in the assay and calculated
as NaBr,
b=percentage content of Cl in the test for chlorides.
Other methods of assay:
1. Argentometry (Мorh method) (see NaCl)
Еm(NaBr) = M. m.
2. Argentometry, back titration (Volhard method)
(see NaCl)
Еm(NaBr) = M.m.
3. Mercurymetry (to see NaCl)
Еm(NaBr) = M.m.
4. Ion-exchange chromatography
The fixed volume of an investigated solution of bromide through a column with
cation exchanger KatН + with speed of 20-25 drops for a minute; wash out
water (50-70 ml) to neutral reaction behind the methyl orange. The filtrate
and washing waters collect in a flask and the received solution титруют 0,1
M of solution NaOH in the presence of methyl orange to transition of
colouring from pink to the yellow:
Kat Н+ + NaBr = Kat Na+ + HBr
HBr + NaOH = NaBr + H2O
Еm(NaBr) = M. m.
STORAGE
In an airtight container .
Action and use
Sedative.
Bromides - demulcents. They can restore balance between
processes of excitation and braking, especially at raised
activation of CNS.
Bromides use at treatment of a neurasthenia, neurosises, a
hysteria, the raised irritability, an epilepsy, a trochee, etc.
Release forms: a powder, tablets - 0,5 g.
Browse: British Pharmacopoeia 2009
SPU, add. 1
General Notices
Potassium Bromide
(Ph Eur monograph 0184)
119.0
KBr
DEFINITION
Content
98.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals.
Solubility
Freely soluble in water and in glycerol, slightly soluble in alcohol.
OBTAINING (see NaBr)
IDENTIFICATION
A. It gives reaction (a) of bromides (2.3.1). (see NaBr)
Bromides:
A. (BrPh, SPU, add. 1 ). Reaction with silver nitrate in the nitric
acid medium.
Other reactions:
B. (BrPh). Reaction with lead dioxide, acetic acid and decolorised
fuchsin solution.
B. Solution S (see Tests) gives the reactions of potassium
(2.3.1). (see KCl)
Potassium and Potassium Salts:
A. (BrPh). Reaction with tartaric acid.
B. (BrPh). Reaction with sodium cobaltinitrite.
Other reaction:
SPU, N. Pyrochemical reaction.
TESTS
Solution S
Dissolve 10.0 g in carbon dioxide-free water R prepared from distilled water R and
dilute to
100 ml with the same solvent.
Bromates –inadmissible impurity.
To 10 ml of solution S add 1 ml of starch solution R, 0.1 ml of a 100 g/l solution of
potassium iodide R and 0.25 ml of 0.5 M sulphuric acid and allow to stand protected from
light for 5 min.
No blue or violet colour develops.
5Br– + BrО3– + 6H+ = 3Br2 + 3H2O
Br2 + KI = 2KBr + I2
Iodides –inadmissible impurity.
To 5 ml of solution S add 0.15 ml of ferric chloride solution R1 and 2 ml of methylene
chlorideR. Shake and allow to separate. The lower layer is colourless
(2.2.2, Method I).
This reaction is not presents:
2I– + 2Fe3+  I2 + 2Fe2+
ASSAY
(BrPh, and SPU, add. 1). Thiocyanatometry.
Dissolve 2.000 g in water R and dilute to 100.0 ml with the same solvent. To
10.0 ml of the solution add 50 ml of water R, 5 ml of dilute nitric acid R, 25.0
ml of 0.1 M silver nitrate and 2ml of dibutyl phthalate R. Shake. Titrate with 0.1
M ammonium thiocyanate, using 2 ml of ferric ammonium sulphate solution R2
as indicator and shaking vigorously towards the endpoint.
1 ml of 0.1 M silver nitrate is equivalent to 11.90 mg of KBr.
KBr + AgNO3 = AgBr + KNO3
AgNO3 + NH4SCN = AgSCN + NH4NO3
3NH4SCN + (NH4)Fe(SO4)2 = Fe(SCN)3 + 2(NH4)2SO4
Еm(KBr) = M. m.
Calculate the percentage content of KBr from the expression:
a – 3.357 b
a=percentage content of KBr and KCl obtained in the assay and calculated as
KBr,
b=percentage content of Cl in the test for chlorides.
Ph Eur
Action and use
Sedative.
Browse: British Pharmacopoeia 2009
SPU, add. 1
General Notices
(Ph Eur monograph 0196)
Sodium Iodide
NaI
149.9
DEFINITION
Content
99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder or colourless crystals, hygroscopic.
Solubility
Very soluble in water, freely soluble in ethanol (96 per cent).
OBTAINING
Analogical to NaBr – from chemical industrial waste – iron(II) iodide and
iron(III) iodide, which heat with Na2CO3:
3Fe + 4I2 = Fe3I8 (FeI2 • 2FeI3)
Fe3I8 + 4Na2CO3 + 4H2O = 8NaІ + Fe(OH)2 + 2Fe(OH)3 + 4CO2
IDENTIFICATION
A. Solution S (see Tests) gives the reactions of
iodides (2.3.1).
Iodides:
A. Reaction with silver nitrate solution in the nitric-acid
medium.
Dissolve a quantity of the substance to be examined equivalent to about 4 mg
of iodide (I–) in 2 ml of water R or use 2 ml of the prescribed solution. Acidify
with dilute nitric acid R and add 0.4 ml of silver nitrate solution R1. Shake and
allow to stand. A curdled, pale-yellow precipitate is formed. Centrifuge and
wash with three quantities, each of 1 ml, of water R. Carry out this operation
rapidly in subdued light disregarding the fact that the supernatant solution
may not become perfectly clear. Suspend the precipitate in 2 ml of water R
and add 1.5 ml of ammonia R. The precipitate does not dissolve.
NaI + AgNO3 → AgI↓ + NaNO3.
curdled, pale-yellow
precipitate
AgI↓ + NH4OH 
B. Reaction with potassium dichromate solution in the
presence of dilute sulphuric acid and chloroform.
To 0.2 ml of a solution of the substance to be examined containing about 5 mg of
iodide (I–) per millilitre, or to 0.2 ml of the prescribed solution, add 0.5 ml of dilute
sulphuric acid R, 0.1 ml of potassium dichromate solution R, 2 ml of water R and 2
ml of chloroform R. Shake for a few seconds and allow to stand. The chloroform
layer is coloured violet or violet-red.
6NaI + K2Cr2O7 + 7H2SO4 → 3I2 + Cr2(SO4)3 + 4Na2SO4 + 7H2O.
Cr2O72– + 14H+ + 6е  2Cr3+ + 7Н2О
2I– – 2е  I2
B. Solution S gives the reactions of sodium (2.3.1). (see
NaCl)
Sodium and Sodium Salts:
A. (BrPh, SPU). Reaction with potassium pyroantimonate
solution.
B. (BrPh, SPU). Reaction with methoxyphenylacetic reagent.
Other reaction:
SPU, N. Pyrochemical reaction.
TESTS
Solution S Dissolve 10.0 g in carbon dioxide-free water R prepared from distilled
water R and dilute to 100 ml with the same solvent.
Iodates and Thiosulphates are inadmissible impurities.
ASSAY
(BrPh, SPU, add. 1). Iodatometry, direct titration.
Dissolve 1.300 g in water R and dilute to 100.0 ml with the same solvent. To
20.0 ml of the solution add 40 ml of hydrochloric acid R and titrate with 0.05
M potassium iodate until the colour changes from red to yellow. Add
5 ml of chloroform R and continue the titration, shaking vigorously, until
the chloroform layer is decolorised.
1 ml of 0.05 M potassium iodate is equivalent to 14.99 mg of NaI.
Indicators of this method:
1. Starch solution.
or 2. Chloroform СНСl3 or tetrachlormethane (phenoxin) CCl4.
IO3– + 6H+ + 6e  I– + 3H2O
E0 = 1,08 В
2IO3– + 12H+ + 10e  I2 + 6H2O
E0 = 1,195 В
5KI + KIO3 + 6HCl = 3I2 + 3H2O
red
2I2 + KIO3 + 6HCl = 5ICl + KCl + 3H2O
yellow
General reaction: 2NaI + KIO3 + 6HCl = 3ICl + KCl + 2NaCl +
3H2O
IO3– + 6H+ + 4e  I+ + 3H2O
I– – 2e  I+
IO3– + 2I– + 6H+  3I+ + 3H2O





Other methods:
1. SP Х. Argentometry (Fajance-Khodacov method), direct
titration.
 Em = М. m.
2. Argentometry (Volhard method), back titration.
 Em = М. m.
3. Mercurymetry.
 Em = М.m.
4. Ion-exchange chromatography.
 Em = М. m.



Protected from light.
Ph Eur
Action and use
Thireoid agent (Iodine drug)
Preparation
Sodium Iodide Injection





STORAGE
Ph Eur

Browse: British Pharmacopoeia 2009
SPU, add. 1
 Potassium

General Notices

(Ph Eur monograph 0186)










Iodide
KI
166.0
DEFINITION
Content
99.0 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white powder or colourless crystals.
Solubility
Very soluble in water, freely soluble in glycerol, soluble in
ethanol (96 per cent).
OBTAINING







Analogical to NaBr – from chemical industrial waste – iron(II)
iodide and iron(III) iodide, which heat with K2CO3:
3Fe + 4I2 = Fe3I8 (FeI2 • 2FeI3)
Fe3I8 + 4К2CO3 + 4H2O = 8КI + Fe(OH)2 +
2Fe(OH)3 + 4CO2
IDENTIFICATION
A. Solution S (see Tests) gives the reactions of iodides
(2.3.1).
B. Solution S gives the reactions of potassium
(2.3.1).




STORAGE
Protected from light.
 Action and use
Antithyroid.
Ph Eur

Browse: British Pharmacopoeia 2009
SPU, add. 1



General Notices
Sodium Fluoride
(Ph Eur monograph 0514)










41.99
NaF
DEFINITION
Content
98.5 per cent to 100.5 per cent (dried substance).
CHARACTERS
Appearance
White or almost white powder or colourless crystals.
Solubility
Soluble in water, practically insoluble in ethanol (96 per cent).

OBTAINING
Sintering of fluor-spar СаF2 with sand SіO2 and sodium carbonate
Na2CO3:

СаF2 + Na2CO3 + SiО2

→ 2NaF + CaSiО3 + CO2



IDENTIFICATION
Reactions for fluoride ions:
A. (BrPh, SPU). Reaction with calcium chloride solution. To 2 ml of solution S (see Tests)
add 0.5 ml of calcium chloride solution R. A gelatinous white precipitate is formed that dissolves on adding 5 ml of ferric chloride solution
R1.

2NaF + CaCl2 = CaF2↓ + 2NaCl
gelatinous white precipitate


B. (BrPh, SPU). Reaction with alizarin S solution and zirconyl
nitrate solution. To about 4 mg add a mixture of 0.1 ml of alizarin S solution R and 0.1 ml of zirconyl nitrate solution R
and mix. The colour changes from red to yellow.
NaF + HCl = HF + NaCl


O
OH
O
OH
2+
SO3



alizarin S
O

OH

red colour
O
ZrOF2
OH
+
SO3Na
O
red colour
O
OH
2

+ 2 NaF
2
zirconyl
nitrate
or 1,2-dioxyanthraquinoneor 3-sodium sulphonate
O
ZrO
SO3Na
+
OH
OH
OH
ZrO(NO3)2
alizarin S
yellow colour
O
2+
ZrO
SO3
+
2 NaNO3
C. (BrPh, SPU). Solution S gives reaction (a) of sodium (2.3.1).
2

ASSAY

(BrPh-2007, SPU).

Acidimetry, non-aqueous titration: To 80.0 mg add a
mixture of 5 ml of acetic anhydride R and 20 ml of anhydrous acetic acid R and heat
to dissolve. Allow to cool and add 20 ml of dioxan R. Using 0.1 ml of crystal violet
solution R as indicator, titrate with 0.1 M perchloric acid until a green colour is
obtained. Carry out a blank titration.
1 ml of 0.1 M perchloric acid is equivalent to 4.199 mg of NaF.

NaF + CH3COOH = (NaFH)+·CH3COO
CH3COOH + HClO4 = CH3COOH2+·ClO4(NaFH)+·CH3COO- + CH3COOH2+·ClO4- = NaClO4 + HF + 2CH3COOH

NaF + HClO4 = NaClO4 + HF










Еm(NaF) = M. m.
 Action
Used in prevention of dental caries.
Preparations
Sodium
Sodium
Sodium
Sodium
Ph Eur
Fluoride
Fluoride
Fluoride
Fluoride
Mouthwash
Oral Drops
Oral Solution
Tablets
and use
Thanks for attention!