LECTURE № 4

Theme: Inorganic metal-containing compounds of Calcium,

Magnesium, Zinc, Copper and Bismuth as drugs

Associate prof. Mosula L.M.

The plan

1. Inorganic drugs of Calcium.2. Inorganic drugs of

Magnesium.3. Inorganic drugs of Zinc.4. Inorganic drugs of Copper.5. Inorganic drugs of Bismuth.

Inorganic drugs of Calcium

Biological action and medical application

Ions Са2 + – formation of bone and tooth tissue; strengthen ability to live

of cages; promote reduction of skeletal muscles and heart

muscles; curlings of blood necessary for improvement.

Calcium preparations1. Calcium oxide (Calcii oxydum) CaО – for preparation of limy water (Aqua calcis).2. Plaster medicinal (Calcii sulfas) 2СаSО4Н2O – for surgery.3. Calcium a carbonate precipitated (Calcii carbonas praecipitatus) СаСО3-at the raised acidity of gastric juice.4. Calcium chloride crystal (we will consider in more details).5. Organic preparations of Calcium (calcium lactate, calcium gluconate, calcium glycerophosphate) will be considered in following lectures.

CALCIUM CHLORIDE HEXAHYDRATE

SPU, addition 1

Calcii chloridum hexahydricum

CaCl26H2O

Calcium chloratum

CALCIUM CHLORIDE DIHYDRATE SPU, addition 1

Calcii chloridum dihydricum CaCl22H2O

Calcium chloratum Not less than 97,0 % and no more than 103,0

% of corresponding substances.

Obtaining 1. Marble processing by chloride acid:

CaCO3 + 2HCl = CaCl2 + CO2 + H2OThe received solution concentrate and clear calcium

chloride CaCl2 of impurity (Fe2 + and Mg2 +) action of chloride acid

HCl (FeCl2 and MgCl2) Elimination: a solution sate with chlorine Cl2:

FeCl2 FeCl3 Precipitation FeCl3 and MgCl2 by

hydrated lime Ca (OH) 2:2FeCl3 + 3Ca (OH) 2 = Fe (OH) 3 + 3CaCl2

MgCl2 + Ca (OH) 2 = Mg (OH) 2 + CaCl2 Filter

The solution is enriched CaCl2. Excess of hydrated lime Ca (OH) 2

delete action of chloride acid HCl:Ca (OH) 2 + 2HCl = CaCl2 + 2H2O

Calcium chloride hexahydricum CaCl26H2O is crystallize out.

2. From solutions which are formed as a waste at soda reception

on Solve method (CaCl2 – a unique by-product in this method).

Properties (SPU, addition 1) The description

CaCl26H2O. Crystal weight of white colour or colourless crystals.

CaCl22H2O. A crystal powder of white colour. Hygroscopic.

Solubility CaCl26H2O. Very soluble in water R, freely soluble in 96 % R.(Freezes at temperature nearby 29).CaCl2H2O. Freely soluble in water Р, soluble in 96 % R.

Because of the big hygroscopicity in drugstores prepare 50 % a solution (Calcium chloratum solutum 50 %), and from this concentrate prepare necessary drugs which contain calcium chloride.

Identification1. Reactions for Calcium-ions Са2 + (see lime chloride, lecture 1):

a) SPU. Interaction with a alcoholic solution of glyoxalhydroxyanil in the

alkaline medium in the presence of chloroform; chloroformic layer is painted in red colour at the expense of

formation of intracomplex compound with Calcium, which extract by chloroform:

b) SPU. Interaction solution of a preparation in acetic acid

with potassium ferrocyanide (II) К4 [Fe (CN) 6] at presence of ammonium chloride NH4Cl; the white crystal precipitate of ammonium-potassium-calcium ferrocyanide (II), insoluble in

acetic acid СН3СООН is formed: Ca2 ++ K + + [Fe (CN) 6] 4- + NH4 + KNH4Ca [Fe (CN) 6].

c) SPU, N. Reaction with ammonium oxalate (NH4) 2C2O4;

the white precipitate, insoluble in dissolved acetic acid СН3СООН and a solution

of ammonia R, soluble in the dissolved mineral acids is formed:

Ca2 + + C2O42 - CaС2O4.

d) SPU, N: Pirochemical reaction. The salt of Calcium wetted with chloride acid R and brought in a colourless flame,

paints it in orange-red colour. Са2 + + h *Са2 + Са2 + + h1

3HNO

3HNO

2. Reactions for chlorides-ions Cl - (acid chloride see, lecture 1)

a) SPU. Reaction with a solution silver nitrate in the presence of nitric acid; the white curdled precipitate is

formedСaCl2 + 2AgNO3 =2

AgCl + Сa (NO3) 2

CL - + Ag + AAgCl + 2NH4OH = [Ag (NH3) 2] Cl + 2H2O

[Ag (NH3) 2] Cl + HNO3 = AgCl + 2NH4NO3

b) Action of oxidizers (К2Cr2O7 (SPU)), in the

presence of sulphatic acid; gas chlorine Cl2 is allocated (to smell it is impossible –

toxicant gas!):

b) Action of oxidizers (К2Cr2O7 (SPU)), in the presence of

sulphatic acid; gas chlorine Cl2 is allocated (to smell it is impossible –

toxicant gas!):3СаCl2 + K2Cr2O7 + 7H2SO4 = 3Cl2 + Cr2 (SO4) 3 + 3СаSO4 +

К2SO4 + 7H2O

Cr2O72 - + 14H + + 6е Cr3 + + 7Н2О

2Cl - – 2е Cl2

Cr2O72– + 6Cl– + 14H+ 2Cr3+ + 3Cl2 + 7Н2О

O CNH NH C6H5

NH NH C6H5

CL2O C

N N C6H5

NH NH C6H5

CL2O C

N N C6H5

N N C6H5-2 HCl -2 HCl

+ +

diphenylcarbazide diphenylcarbazone diphenylcarbadiazone (Colourless) (orange-yellow) (violet-red)

Tests1.Aluminium (an inadmissible impurity).

2.To solution S add a solution of ammonium chloride R, solution of ammonia dissolved R1 and heat up to boiling;

the solution should not cloud and the precipitate should not be formed:

Al3+ + 3NH4OH Al(OH)3 + 3NH4+2. Barium (an inadmissible impurity).

To solution S add a solution calcium of sulphate R; opalescence the received solution is not more intense

than that in a mix of solution S and water:Ва2 + + SO42 - ВaSO4

ASSAY1. SPU. Chelatometry, direct titration Titrant – a standard solution of sodium EDTA (ethylenediaminetetraacetate acid) (Na2–EDTA) Medium– the concentrated solution of sodium hydroxide NаOH Indicator – indicator mix of calconcarbonic acidTitrate test solution before change of colouring with violet to dark blue.

Chemism: At addition to test solution of calcium chloride of

indicator mix of calconcarbonic acid H2Ind (dark blue colouring) the complex metal-indicator CaInd (red-violet colour) is

formed:CaCl2 + H2Ind = CaInd + 2HCl

dark blue violet.At titration of such solution by standard solution Na-

edetate in the environment of the concentrated solution

sodium hydroxide NаOH (рН 7) is formed very strong colourless soluble in water a

complex of ions Са2 + with Na-edetate under the scheme:

CH2 N

CH2

N

CH2COONa

CH2COOH

CH2COOH

CH2COONa

Ca

CH2COONa

CH2COOCH2 N

CH2

NCH2COO

CH2COONa

Ca2+

+ + 2 H+

Superfluous drop Na2-EDTA destroys complex CaInd, forming complex

Ca-edetat and free indicator H2Ind of dark blue colour.

Violet dark blue Em (CaCl26H2O) = М m.

CH2 N

CH2

N

CH2COONa

CH2COOH

CH2COOH

CH2COONa

Ca Ind Ca

CH2 N

CH2

NCH2COO

CH2COONa

CH2COONa

CH2COO+ + H2 Ind

+H+

Chelatomerty in the pharmaceutical analysis (SPU)Titrant – sodium EDTA (sodium salt of

ethylenediaminetetraacetate acid) (Na2-EDТА)

Test ionConditions of carrying

out of experimentIndicator mix Colouring change

Bi3 +

Solution NH3 conc.

before clouding occurrence, then HNO3 before

disappearance of clouding, t = 70 C

Xylenol orange (1 part. + 99 parts of KNO3)

pink-violet to yellow

Ca2 + Solution NаОH conc.

calconcarbonic acid

(1 part + 99 parts of NaCl)

Violet in dark blue

Mg2 +

Ammoniac buffer solution

pН 10,0, t 40 C

Eriochrome black

(1 part + 99 parts of NaCl)

Violet in dark blue

Pb2 + hexamethylenetetramine (the alkaline medium) pH~7,8–8,2

Xylenol orange (1 part + 99 parts of

NaCl)

Violet-red in the yellow

Zn2 + hexamethylenetetramine (the alkaline medium) pH~7,8–8,2

Xylenol orange (1 part. + 99 parts of KNO3)

Violet-red in the yellow

Al3 +

Back chelatometry, excess Na2-EDТА titrate of standart

solution of Pb (NO3) 2

Xylenol orange (1 part. + 99 parts of KNO3)

pink-violet

Hg2 +

Back chelatometry, excess Na2-EDТА titrate of standart

solution of ZnSO4

Eriochrome black (1 part + 99 parts of

NaCl)The violet

2. Argentometry (Моrh method), direct titration Titrant – a standard solution of silver nitrate AgNO3;

Medium – neutral (!) Indicator – a solution of potassium chromate K2CrО4.

Titrate before occurrence of orange-red colour of precipitate

1СаCl2 + 2AgNO3 = 2AgCl + Сa (NO3) 2The superfluous drop of AgNO3 co-operates with

the indicator with formation of precipitate of orange-red colour Ag2CrО4:

2AgNO3 + K2CrО4 = Ag2CrО4 + 2KNO3Em (CaCl26H2O) = М m./2

3. Oxalic method It is based on such processes:

Quantitative precipitation of Calcium-ions:

Са2 + + С2О42–СCаС2О4 Precipitate dissolution in dissolved sulphatic acid H2SO4

СаС2О4 + 2Н+ Са2+ + Н2С2О4;

Titration oxalate acid Н2С2О4, which was formed

(its quantity is equivalent to an investigated preparation of Calcium),

by standard solution of potassium permanganate KMnO4

2KMnО4 + 5Н2С2О4 + 3H2SO4 = 2MnSO4 + 10CO2 + K2SO4 + 8H2O

MnО4–+ 8H + + 5 e Mn2 + + 4H2O | 5 | 2 H2С2O4 – 2e 2СО2 + 2H + | 2 | 5

5H2С2O4 + 2MnО4– + 6H+ 2Mn2+ + 10СО2 + 8H2O

Em (CaCl26H2O) = М m./2

Storage. In the air-tight container.Store in a dry place, in the glasswares which

stoppers fill in with paraffin, considering high hygroscopicity. Therefore in drugstores prepare

a concentrate – 50 % a solution (Calcium chloratum solutum 50 %) which cultivation receive solutions of

a preparation of necessary concentration.Marks. In necessary cases mark:

the substance is suitable for manufacture of

solutions for a dialysis.Application, Anti-inflammatory, antiallergic,

hemostatic means.Accept oral or enter intravenously

on 5–15 ml of 10 % of a solution (contains СаCl26H2O – 100 ml,

waters for injections – to 1L). At introduction hypodermically or

intramuscularly causes necrosis tissue (!).

Inorganic drugs of Magnesium MAGNESIUM OXYDE, HEAVY SPU Magnesii oxydum ponderosum MAGNESIUM OXYDE, LIGHTSPUMagnesii oxydum leve MAGNESIUM OXYDEMagnesii oxydum MgО Маgnеsіuм oxydatumМаgnеsіа ustaNot less than 98,0 % and no more than 100,5 % MgО, in recalculation on the fried substance.

Obtaining1. Thermal processing of magnesium carbonate

basic: 3MgCO3Mg (OH) 23H2O 4

t

MgО + 3CO2 + 4H2O

t 250–300 C. 2. From a brine (pickle) at processing of

potash salts which contain MgCl2

a) To a brine add limy milk Ca (OH) 2 for

sedimentation of impurity Fe2 + and Fe3 +:Fe2 + + 2ON - F e (OH) 2Fe2 + + 3ON - F e (OH) 3

And sulphatic acid H2SO4 for binding

(linkage) of Calcium-cations Ca2 +:SO4

2 - + Ca2 + C aSO4

b) Excess of limy milk Ca (OH) 2 binding of

magnesium chloride MgCl2 in a kind magnesium

hydroxide Mg (OH)2:,

MgCl2 + Ca (OH) 2 = Mg (OH) 2 + CaCl2

c) Calcination of magnesium hydroxide (500C) to magnesium oxide MgО:

C0500tMg (OH) 2 M gO + H2O

3. Processing of magnesium chloride superheated water steam:

MgCl2 + H2О = MgО + 2НCl

PropertiesThe description (SPU)

Magnesium oxide heavy is fine powder of white colour.

Magnesium oxide light – finel amorphous powder of white colour.

Solubility. Are practically insoluble in water R, in which find out alkaline reaction with phenolphthalein.

(Are soluble in the dissolved acids.)

Cl4NH

N

OH

N

O Mg

N

O

2 + MgCl2

NH4OH

NH4Cl+ 2 HCl

Identification Reactions for Magnesium-ions Mg2 + (after dissolution substance

in nitric acid dissolved R HNO3

and neutralisations by a solution sodium гидроксида dissolved Р NаOH). MgО + 2HNO3 = Mg (NO3) 2 + H2O

a)SPU. Reaction with sodium hydrogenphosphate in theb) presence of ammonia solution and ammonium chloride

Mg2 + + HPO42 - + NH4ОН NH4MgPO4 + Н2О white precipitate

b) Reaction with 8-oxyquinoline in the medium of an ammoniac buffer solution;the yellow- green crystal precipitate of magnesium 8-oxyquinoline is formed:

Tests

1. Inadmissible specific impurity are not present.

ASSAYShot of magnesium oxide preliminary dissolve inchloride acid dissolved R and dilute by water R:

MgO + 2HCl = MgCl2 + H2O1. SPU. Chelatometry, direct titration (see the

table)Em (MgО) = М m.

2. The acid-base titration, back titration In the presence of methyl orange colouring before

transition from pink to the yellow.1MgО + 2HCl = MgCl2 + H2O

excess2HCl + 2NaOH = 2NaCl + 2H2O

1 mol MgО 2 mol (2 equivalent) HCl 2 mol (2 equiv.) NaOH

Therefore Em (MgO) = М m./2

Storage. In densely corked container.Application. Antiacid agent.

MgO neutralizes chloride acid of gastric juice, magnesium

oxide turns in magnesium chlorideMgO + 2HCl = MgCl2 + H2O

which finds out laxative effect. The release form: a powder and

tablets for 0,5 g. Is a part of preparations of

“Almagel”, “Gastal”, and also an antidote at a

poisoning with acids.

MAGNESIUM CARBONATE, HEAVY SPU, add. 1

Magnesii subcarbonas ponderosus

MAGNESIUM CARBONATE,

LIGHT SPU, add. 1 Magnesii subcarbonas

levis

MAGNESIUM CARBONATE ALKALINE (BASIC) NMagnesii subcarbonas

Magnesia alba Magnesium subcarbonicum

3MgCO3Mg (OH) 23H2O

t

t

Obtaining1. Interaction of solutions of magnesium sulphate and

sodium carbonate (70-80):

4MgSO4 + 4Na2CO3 + 4H2O 3MgCO3Mg (OH) 23H2O + 4Na2SO4 + CO2

2. Thermal decomposition of magnesium hydrogencarbonate:

4Mg (HCO3) 23 MgCO3Mg (OH) 23H2O + 5CO2

PropertiesThe description

SPU, add. 1. A powder of white colour. Solubility

SPU, add. 1. It is practically insoluble in water R.

(It is dissolved in the dissolved acids with rough allocation of bubles of gas)

3MgCO3Mg (OH) 23H2O + 8HCl = 4MgCl2 + 3CO2 + 8H2O

It is much easier dissolved in water which contains CO2, forming magnesium hydrogencarbonate:

3MgCO3Mg (OH) 23H2O + 5CO2 = 4Mg (HCO3) 2It is possible to express this process

to such simplified equations:MgCO3 + H2O + CO2 = Mg (HCO3) 2

Therefore magnesium hydrogencarbonate is a component of many mineral waters.

At standing a transparent solution magnesium hydrogencarbonate

again cloud as a result of decomposition reaction:Mg(HCO3)2 MgCO3 + H2O + CO2

Identification1. SPU, add. 1. Bulk volume

15 g substances of magnesium carbonate heavy are

occupied with volume about 30 ml. 15 g substances of magnesium carbonate light are

occupied with volume about 180 ml.Test for identity of magnesium carbonate

of the core spend:3MgCO3Mg (OH) 23H2O + 8HCl = 4MgCl2 + 3CO2 +

8H2O2. Reactions for Magnesium-ions Mg2 +

(after preliminary dissolution in the dissolved acids) (see magnesium oxide).

3. Reactions for carbonate-anions СО32–: a)SPU, interaction with mineral acids (SPU – acetic acid

dissolved R СН3СООН):СО32– + 2СН3СООН = 2СН3СОО– + Н2О + СО2

Gas, which is allocated (without colour and a smell), pass through a solution barium hydroxide R Ва (OH)2;

the white precipitate, which is dissolved a lot of chloride acid R1 HCl is formed.

СО2 + Ва (OH) 2 = ВаСО3 + Н2ОВаСО3 + 2HCl = BaCl2

b) SPU, N. Reaction with the sated solution of magnesium

sulphate At addition to a water solution of a substance, which contains anions of

СО32–, sated solution of magnesium sulphate R MgSO4 at room temperature is formed white precipitate MgCO3 (difference hydrogencarbonate,

which form a precipitate only at boiling):CO32 - + Mg2 + = MgCO3

Tests1. N. An inadmissible impurity – Barium.

Ва2 + + SO42 - B aSO4

ASSAY Shot of test substance dissolve in chloride acid хлоридной diluted R

HCl 3MgCO3Mg (OH) 23H2O + 8HCl = 4MgCl2 + 3CO2 + 8H2Osoluble with water R and spend quantitative definition (MgCl2)

similarly magnesium oxide (see above).

1.SPU. Chelatometry, direct titration (see magnesium oxide)

As the preparation structure is not constant, recalculation do on the maintenance magnesium oxide MgО.

Em (MgО) =М. M.

2. The acid-base titration, back titration (similarly magnesium oxide).

Em (MgО) = М m./2

%100)3)(3(

)(%

223

OHOHMgMgCOm

FMgOm

.)MgO(M4

)OH3)OH(MgMgCO3(MF 223

3. Gravimetric (weight) method Shot of magnesium carbonate alkaline 3MgCO3Mg (OH) 23H2O

dry up, calcinate to constant weight and weigh (weight or gravimetric form –

MgО):

3MgCO3Mg (OH) 23H2O

= 4MgО + 3СО2 + 4Н2О

Calculate the maintenance of magnesium oxide MgО in a preparation under the formula:

,

Where F – gravimetric factor, which calculate under the formula:

Maintenance МgO should be less than 40,0 % and no more than 45 %.

Storage. In densely corked container.Application. Antiacid agent.

Release forms: a powder and tablets which contain magnesium

carbonate alkaline (0,5 g) and sodium a hydrocarbonate (0,5 g).

Is a part of tablets “Vicalinum”, “Vicairum”.

MAGNESIUM SULPHATE HEPTAHYDRATE

SPU, add. 1Magnesii sulfas heptahydricus MAGNESIUM SULPHATE Magnesii sulfas Magnesium sulfuricum Sal amarum Bitter salt Epson salt

MgSO47H2O Not less than 99,0 % and no more than 100,5 % MgSO4 (М m. =

120,4 g/mol)

Obtaining1.Dissolution of magnesite MgCO3 a lot of hot

dissolved sulphatic acid H2SO4:

MgCO3 + H2SO4 = MgSO4 + CO2 + H2OSolution filter, evaporate before crystallisation;

thus receive epsom salt – MgSO47H2O. The filtered crystals recrystallization

from water.Properties

The description. SPU, add. 1. A crystal powder of white colour

or brilliant colourless crystals. Solubility. SPU, add. 1. Freely soluble in water

R, very soluble in boiling water R, it is practically

insoluble in 96 % alcohol R.

PropertiesThe description. SPU, add. 1. A crystal powder of

white colour or brilliant colourless crystals. Solubility. SPU, add. 1. Freely soluble in water R,

very soluble in boiling water R, it is practically insoluble in 96 % alcohol R.

Identification1. Reactions for Magnesium-ions Mg2 + (see

magnesium oxide):2. Reactions for sulphate-anions SO42 –

(see sodium sulphate, lecture 2):a)SPU. Reaction with solution of barium chloride

ВаCl2 in chloride-acid medium HCl; white precipitate ВаSO4 is formed: MgSO4 + BaCl2 = BaSO4 + MgCl2

whiteSO42 - + Ва2 + ВаSO4

The white precipitate is insoluble in mineral acids and alkalis.

SPU. To the suspension, received in reaction a), add a solution of iodine I2; yellow colouring does not

disappear (difference from sulphites SO32 - and dithionites S2O32–), but becomes colourless at addition by drops of solution

tin (ІІ) chloride SnCl2 (difference from iodates IO3–). A mix boil; the deposit does not become colourless

(difference from selenates and wolframates):MgSO4 + I2 (iodine does not become colourless).

I2 + SnCl2 + 4HCl = 2HI + H2 [SnCl6] (iodine becomes colourless).

TestsAs magnesium sulphate MgSO47H2O apply

for parenteral introductions, and also inside and in considerable quantities therefore especial requirements

to its cleanliness are put. 1.Solution S. The substance solution in water R

2.should be clear and colourless.2. Acidity or alkalinity.

ASSAY SPU. Chelatometry (see magnesium

oxide)Em (MgSO4) = М m.

Storage. In hermetically corked container because easily disappears.

ApplicationMagnesium sulphate has versatile influence on an

organism. 1. At intake as a laxative.

2. At parenteral introduction - restful action on the central nervous system.

3. In the form of 25 % of a solution enter hypodermically as antispasmodic.4. Apply to a labour pain relief, as

anticonvulsant intramuscularly on 5–20 ml of 25 % of a solution.

In case of redispensing of magnesium sulphate enter

intravenously 10 % a solution of calcium chloride (antagonists).

Release forms: a powder, 20 % or 25 % asolution in ampoules 5, 10 or 20 ml.

MAGNESIUM CHLORIDE HEXAHYDRATE SPU, add. 1

Magnesii chloridum hexahydricum

MgCl26H2O

Not less than 99,0 % and no more than 100,5 % MgCl26H2O.

PropertiesThe description. Colourless crystals. Hygroscopic.

Solubility. Very soluble in water R, freely soluble in 96 % alcohol R.

Identification 1. Definition of water by semimicromethod (Fisher's method).

Iodometric definition of a moisture. The maintenance of water from 51,0 % to 55,0 %. Fisher's reagent is a solution of sulphur dioxide SO2, iodine

I2 and pyridine C5H5N in a methanol. At the heart of a method oxidation

SO2 by means of iodine I2 in the presence of water lays:

SO2 + I2 + 2Н2О H2SO4 + 2HI

Reaction needs to be spent at presence pyridine, which as the mild base , connects (binds) HI and SO2 in nonvolatile compounds:

N N+

H

I

N+

SOO

O

N+

SOO

O

N+

H

CH3SO4

3 + I2 + SO2 + H2O 2 +

-+ CH3OH

The titration end define visually on change of colouring from ellow to red-brown or by means of potentiometry.

2. Reactions for Magnesium-ions Mg2 + (see magnesium oxide):3. Reactions for chlorides-ions Cl - (see calcium chloride):

a)SPU. Reaction with a solution of silver nitrate in the presence of nitric acid; the white curdled precipitate is formed;

b) SPU. Action of potassium dichromate К2Cr2O7 in the sulphatic-acid medium;

gas chlorine Cl2 which paints the filtering paper moistened of diphenylcarbazide, in violet-red colour is allocated.

Tests1. Solution S prepared by dissolution test substance in water,

free from СО2, R, should be clear and colourless.2. Acidity or alkalinity.

4. Potassium. (not more than 500 ppm).5. Aluminium. (not more than 1 ppm).

6. N. An inadmissible impurity – Barium:Ва2 + + SO42 - BaSO4

white precipitateASSAY

SPU. Chelatometry (see magnesium sulphate).Em (MgCl26H2O) = М m.

StorageIn the air-tight container.

MarksIn necessary cases mark:

The substance is suitable for manufacture of solutions for perenteral dialysis, a hemodialysis or a haemofiltration;

The substance is suitable for manufacture of drugs for parenteral applications.

Thanks for attention!