LECTURE LECTURE № № 66

Salts of carboxylic acids and saturated Salts of carboxylic acids and saturated aminoacids aliphatic series as drugsaminoacids aliphatic series as drugs

Associate prof. Mosula L. M.Associate prof. Mosula L. M.

The plan

1. Salts of carboxylic acids as drugs: potassium acetate, calcium lactate, sodium hydroxybutyrate, sodium citrate, calcium gluconate.

2. The saturated aminoacids of aliphattic series: glutamic acid, cysteine hydrochloride, acetylcysteine, methionine, aminalonum.

Salts of carboxylic acids as drugsSalts of carboxylic acids as drugs Potassium acetatePotassium acetate

CH3COOKCH3COOK Description. Description. Potassium acetate is a Potassium acetate is a

white crystalline powder; it is a slightly white crystalline powder; it is a slightly hydroscopic with characteristic odor of hydroscopic with characteristic odor of acetic acid and salty test.acetic acid and salty test.

Solubility.Solubility. It is soluble in water and It is soluble in water and alcohol.alcohol.

Identification.Identification. A.A. Yields the reaction characteristic of Yields the reaction characteristic of

potassium salts:potassium salts:

B.B. Yields the reactions characteristic Yields the reactions characteristic of carboxylic acids: reacts with ethyl of carboxylic acids: reacts with ethyl alcohol to form ether:alcohol to form ether:

C.C. Acetate-ion reacts with iron (III) Acetate-ion reacts with iron (III) chloride solution to form a red chloride solution to form a red complex:complex:

K+ + HOOC-(CHOH)2-COOH HOOC-(CHOH)2-COOK H++

wine acid

2CH3COOK H2SO4 C2H5OH CH3COOC2H5 K2SO4+ + 2 2 2H2O+ +

3FeCl3 9+ CH3COOK 2+ H2O [(CH3COO)6Fe3(OH)2]+CH3COO-

+ CH3COOH2 9+ KCl

AssayAssay.. Carry out a water-free titration. Dissolve the Carry out a water-free titration. Dissolve the exact amount of potassium acetate in ice acetic acid and exact amount of potassium acetate in ice acetic acid and titrate with 0.2N hydrochloric acid use a crystalline-violet as titrate with 0.2N hydrochloric acid use a crystalline-violet as an indicator.an indicator.

Potassium acetate is indicated for the treatment and Potassium acetate is indicated for the treatment and prevention of potassium deficiency. It also finds usefulness prevention of potassium deficiency. It also finds usefulness as a diuretic substance.as a diuretic substance.

CH3COOK + CH3COOH (CH3COOKH)+ * CH3COO-

CH3COOH + HClO4 (CH3COOH2)+* ClO4

-

(CH3COOKH)+ * CH3COO-+ (CH3COOH2)

+* ClO4

- KClO4 CH3COOH

+

3

CH3COOK + HClO4 KClO4 CH3COOH

Sodium γ -oxibutyrateSodium γ -oxibutyrate HOCH2CH2CH2COONaHOCH2CH2CH2COONa

It occurs as white or slightly yellow It occurs as white or slightly yellow crystalline powder with characteristic odor.crystalline powder with characteristic odor.

Identification.Identification. A.A. Yields a reaction characteristic of sodium salts. Yields a reaction characteristic of sodium salts. B.B. Sodium oxibutyrate reacts with hydrochloric acid to form γ- Sodium oxibutyrate reacts with hydrochloric acid to form γ-

butyrolactone. Extract synthesized γ-butyrolactone with ether butyrolactone. Extract synthesized γ-butyrolactone with ether

and identify by refractive index (1.4280-1.4360).and identify by refractive index (1.4280-1.4360).

AssayAssay.. Cary out a water-free titration as for Cary out a water-free titration as for assay of potassium acetate.assay of potassium acetate.

HOCH2CH2CH2COONa + HCl

O O

+ + H2ONaCl

Sodium citrateSodium citrate (Sodium hydrocitrate for injection)(Sodium hydrocitrate for injection) It is a white crystalline powder or colorless crystals, odorless It is a white crystalline powder or colorless crystals, odorless

with salty test. with salty test. Identification.Identification. A.A. Yields the reaction characteristic of sodium salts: Yields the reaction characteristic of sodium salts:

B.B. Sodium citrate reacts with calcium chloride to form Sodium citrate reacts with calcium chloride to form calcium salt that is insoluble in boiling water:calcium salt that is insoluble in boiling water:

Calcium citrate that is obtained is soluble in hydrochloric Calcium citrate that is obtained is soluble in hydrochloric acid.acid.

Na++ Zn[(UO2)3(CH3COO)8] + CH3COOH 9+ H2O NaZn[(UO2)3(CH3COO)9] * 9 H2O H+

+

CH2 COONa

C COONa

CH2 COONa

HO2 3+ CaCl2

CH2 COO-

C COO-

CH2 COO-

HO

2

Ca2 +

3

3

-

+ NaCl6

AssayAssay.. Carry out a neutralization Carry out a neutralization titration after ion exchange titration after ion exchange chromatography.chromatography.

Titrate obtained citrate acid with 0.05M Titrate obtained citrate acid with 0.05M potassium or sodium hydroxide.potassium or sodium hydroxide.

4% solution of calcium citrate is used 4% solution of calcium citrate is used for protection of blood coagulation.for protection of blood coagulation.

CH2 COONa

C COONa

CH2 COONa

HO + 3 [Kat]-H+ [Kat]-Na+3 +

CH2 COOH

C COOH

CH2 COOH

HO

Calcium gluconateCalcium gluconate ObtainingObtaining The gluconic acid used in the preparation of calcium The gluconic acid used in the preparation of calcium

gluconate can be prepared by electrolytic oxidation of glucose gluconate can be prepared by electrolytic oxidation of glucose as follows:as follows:

Gluconic acid is produced on a commercial scale by the action Gluconic acid is produced on a commercial scale by the action of a number of fungi bacteria, and molds upon 25% to 40% of a number of fungi bacteria, and molds upon 25% to 40% solutions of glucose. The fermentation is best carried out in solutions of glucose. The fermentation is best carried out in the presence of calcium carbonate and oxygen to give almost the presence of calcium carbonate and oxygen to give almost quantitative yields of gluconic acid. The fermentation is quantitative yields of gluconic acid. The fermentation is complete in 8 to 18 days. complete in 8 to 18 days.

C

C

C

C

C

CH2OH

H

H

H

H

H

OH

OH

OH

HO

OCOO-

C

C

C

C

CH2OH

H

H

H

H

OH

OH

OH

HONaBrCaCO3

Carbon electrodes

Ca2 +

D - Glucose Calcium gluconate2

ProrertiesProrerties.Calcium gluconate occurs as a white crystalline or .Calcium gluconate occurs as a white crystalline or granular powder, without odor or test. Its solutions are neutral granular powder, without odor or test. Its solutions are neutral to litmus paper. to litmus paper.

Solubility . Solubility . One gram of calcium gluconate dissolves slowly One gram of calcium gluconate dissolves slowly in about 30 ml of water and in 5 ml of boiling water. It is in about 30 ml of water and in 5 ml of boiling water. It is insoluble in alcohol and in many organic solvents. insoluble in alcohol and in many organic solvents.

The mineral acids that are stronger than gluconic acid will The mineral acids that are stronger than gluconic acid will decompose calcium gluconate. It is incompatible with soluble decompose calcium gluconate. It is incompatible with soluble sulphates, carbonates, bicarbonates, citrates, tartrates, sulphates, carbonates, bicarbonates, citrates, tartrates, salicylates and benzoates.salicylates and benzoates.

Identification.Identification. A.A. Calcium gluconate solution yields the reaction Calcium gluconate solution yields the reaction

characteristic for calcium salts.characteristic for calcium salts. B.B. Solution reacts with iron chloride in neutral Solution reacts with iron chloride in neutral

medium to form green complex.medium to form green complex.

+

(CH2OH-(CHOH)4-COO-)2Ca9 2++ + H2OFeCl3 [(CH2OH-(CHOH)4-COO)6Fe3(OH)2]+CH2OH-(CHOH)4-COO-

+

CH2OH-(CHOH)4-COOH + 94

6CaCl2

Assay.Assay. Dissolve 0.4 g in 20 ml of water. Cool and add 10 ml of Dissolve 0.4 g in 20 ml of water. Cool and add 10 ml of ammonium buffer solution, and 0.1 g of chromium-blue as an ammonium buffer solution, and 0.1 g of chromium-blue as an indicator, and titrate with 0.05M EDTA antill indicator, and titrate with 0.05M EDTA antill blue-violet colorblue-violet color is is obtained.obtained.

OH

SO3Na

OH

++

+ +

CH2

CH2

N

N

CH2COONa

CH2COONa

CH2COOH

CH2COOH

+CH2

CH2

N

N

CH2COONa

CH2COONa

CH2COO

CH2COOCa +

CH2

CH2

N

N

CH2COONa

CH2COONa

CH2COOH

CH2COOH

+

CH2

CH2

N

N

CH2COONa

CH2COONa

CH2COO

CH2COOCa +

bluecolorless

colorless

N N

OH

NaO3S

NN

OCa

SO3NaNaO3S

OHO

H2OH2O

pink

NH4OH H2O

2

NN

OCa

SO3NaNaO3S

OHO

H2OH2O

NN

OH

SO3NaNaO3S

OHOH

-violet

blue

pink

(CH2OH-(CHOH)4-COO-)2Ca

+ 2 CH2OH-(CHOH)4-COOH

CH2OH-(CHOH)4-COOH CH2OH-(CHOH)4-COONH4

(CH2OH-(CHOH)4-COO-)2Ca CH2OH-(CHOH)4-COOH

+ +NH4OH H2OCH2OH-(CHOH)4-COOH CH2OH-(CHOH)4-COONH4

Each ml of 0.05M EDTA is equivalence to Each ml of 0.05M EDTA is equivalence to 0.02242 g of calcium gluconate.0.02242 g of calcium gluconate.

Calcium gluconate fills the need for a soluble Calcium gluconate fills the need for a soluble nontoxic well-tolerated form of calcium that nontoxic well-tolerated form of calcium that can be employed orally, intramuscularly, or can be employed orally, intramuscularly, or intravenously. Calcium therapy is indicated in intravenously. Calcium therapy is indicated in conditions such as parathyroid deficiency conditions such as parathyroid deficiency (tetany), general calcium deficiency, and (tetany), general calcium deficiency, and when calcium is the limiting factor in when calcium is the limiting factor in increased clotting time of the blood. It can be increased clotting time of the blood. It can be used both orally and intravenously.used both orally and intravenously.

Amino Acids as drugsAmino Acids as drugs Proteins are essential components of all living Proteins are essential components of all living

matter. As cellular components, proteins perform matter. As cellular components, proteins perform numerous functions. The chemical reactions numerous functions. The chemical reactions fundamental to the life of the cell are catalyzed by fundamental to the life of the cell are catalyzed by proteins called enzymes. Other proteins are proteins called enzymes. Other proteins are structural constituents of protoplasm and cell structural constituents of protoplasm and cell membranes. Some hormones are characterized as membranes. Some hormones are characterized as proteins or proteinlike compounds because of their proteins or proteinlike compounds because of their polypeptide structural features.polypeptide structural features.

Proteins are biosynthesized from α-amino acids, Proteins are biosynthesized from α-amino acids, and when proteins are hydrolyzed, amino acids are and when proteins are hydrolyzed, amino acids are obtained. Some very complex (conjugated) obtained. Some very complex (conjugated) proteins yield other hydrolysis products in addition proteins yield other hydrolysis products in addition to amino acids. α-Amino acids are commonly to amino acids. α-Amino acids are commonly characterized with the generalized structure:characterized with the generalized structure:C COOHR

H

NH2

The relative high melting point, The relative high melting point, solubility, behavior, and acid-base solubility, behavior, and acid-base properties characteristic of amino properties characteristic of amino acids can be accounted for on the acids can be accounted for on the basis of the dipolar ion structure basis of the dipolar ion structure (commonly called zwitterion). Amino (commonly called zwitterion). Amino acids in the dry solid state are dipolar acids in the dry solid state are dipolar ions (inner salts). Amino acids when ions (inner salts). Amino acids when dissolved in water can exist as dipolar dissolved in water can exist as dipolar ions.ions.

Glutamic acidGlutamic acid (Ph Eur monograph 0750)(Ph Eur monograph 0750)

C5H9NO4C5H9NO4     147.1 147.1    56-86-056-86-0 Action and use Action and use Amino acid. Amino acid. Ph Eur Ph Eur DEFINITIONDEFINITION Glutamic acid contains not less than 98.5 per cent and not more than the equivalent Glutamic acid contains not less than 98.5 per cent and not more than the equivalent

of 100.5 per cent of (2of 100.5 per cent of (2SS)-2-aminopentanedioic acid, calculated with reference to the )-2-aminopentanedioic acid, calculated with reference to the dried substance. dried substance.

CHARACTERSCHARACTERS A white, crystalline powder or colourless crystals, freely soluble in boiling water, A white, crystalline powder or colourless crystals, freely soluble in boiling water,

slightly soluble in cold water, practically insoluble in acetic acid, in acetone and in slightly soluble in cold water, practically insoluble in acetic acid, in acetone and in alcohol. alcohol.

IDENTIFICATIONIDENTIFICATION First identificationFirst identification  A, BA, B. . Second identificationSecond identification  A, C, DA, C, D. .   A. It complies with the test for specific optical rotation (see A. It complies with the test for specific optical rotation (see

Tests). Tests).   B. Examine by infrared absorption spectrophotometry B. Examine by infrared absorption spectrophotometry

(2.2.24)(2.2.24), comparing with the spectrum obtained with , comparing with the spectrum obtained with glutamic acid CRSglutamic acid CRS. Examine the substances prepared as . Examine the substances prepared as discs. If the spectra obtained show differences, dissolve the discs. If the spectra obtained show differences, dissolve the substance to be examined and the reference substance substance to be examined and the reference substance separately in the minimum quantity of separately in the minimum quantity of water Rwater R, evaporate to , evaporate to dryness at 60 °C and record new spectra using the residues. dryness at 60 °C and record new spectra using the residues.

  

C. Examine the chromatograms obtained in the test for C. Examine the chromatograms obtained in the test for ninhydrin-positive substances. The principal spot in the ninhydrin-positive substances. The principal spot in the chromatogram obtained with test solution (b) is similar chromatogram obtained with test solution (b) is similar in position, colour and size to the principal spot in the in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a). chromatogram obtained with reference solution (a).

  D. To 2.0 ml of solution S (see Tests) add 0.1 ml of D. To 2.0 ml of solution S (see Tests) add 0.1 ml of

phenolphthalein solution Rphenolphthalein solution R and 3.0 ml to 3.5 ml of and 3.0 ml to 3.5 ml of 1 M 1 M sodium hydroxidesodium hydroxide to change the colour of the indicator to change the colour of the indicator to red. Add a mixture of 3 ml of to red. Add a mixture of 3 ml of formaldehyde solution formaldehyde solution RR, 3 ml of , 3 ml of carbon dioxide-free water Rcarbon dioxide-free water R and 0.1 ml of and 0.1 ml of phenolphthalein solution Rphenolphthalein solution R, to which sufficient , to which sufficient 1 M 1 M sodium hydroxidesodium hydroxide has been added to produce a pink has been added to produce a pink colour. The solution is decolourised. Add colour. The solution is decolourised. Add 1 M sodium 1 M sodium hydroxidehydroxide until a red colour is produced. The total until a red colour is produced. The total volume of volume of 1 M sodium hydroxide1 M sodium hydroxide used is 4.0 ml to 4.7 used is 4.0 ml to 4.7 ml. ml.

TESTSTESTS Solution S Solution S Dissolve 5.00 g in Dissolve 5.00 g in 1 M hydrochloric acid1 M hydrochloric acid with gentle heating, with gentle heating,

and dilute to 50.0 ml with the same acid. and dilute to 50.0 ml with the same acid. Appearance of solution Appearance of solution Solution S is clear Solution S is clear (2.2.1)(2.2.1) and colourless and colourless (Method II, 2.2.2)(Method II, 2.2.2). . Specific optical rotation Specific optical rotation (2.2.7)(2.2.7) + 30.5 to + 32.5, determined on solution S and calculated + 30.5 to + 32.5, determined on solution S and calculated

with reference to the dried substance. with reference to the dried substance. Ninhydrin-positive substances Ninhydrin-positive substances Examine by thin-layer chromatography Examine by thin-layer chromatography (2.2.27)(2.2.27), using a , using a TLC TLC

silica gel plate Rsilica gel plate R. .

Chlorides Chlorides (2.4.4)(2.4.4) Dissolve 0.25 g in 3 ml of Dissolve 0.25 g in 3 ml of dilute nitric acid Rdilute nitric acid R and dilute to 15 ml with and dilute to 15 ml with water Rwater R. The . The

solution, to which 1 ml of solution, to which 1 ml of water Rwater R is added instead of is added instead of dilute nitric acid Rdilute nitric acid R, complies with , complies with the limit test for chlorides (200 ppm). the limit test for chlorides (200 ppm).

Sulphates Sulphates (2.4.13)(2.4.13) Dilute 5 ml of solution S to 15 ml with Dilute 5 ml of solution S to 15 ml with distilled water Rdistilled water R. The solution complies with the . The solution complies with the

limit test for sulphates (300 ppm). limit test for sulphates (300 ppm). Ammonium Ammonium (2.4.1)(2.4.1) 50 mg complies with limit test B for ammonium (200 ppm). Prepare the standard 50 mg complies with limit test B for ammonium (200 ppm). Prepare the standard

using 0.1 ml of using 0.1 ml of ammonium standard solution (100 ppm NH4) Rammonium standard solution (100 ppm NH4) R. . Iron Iron (2.4.9)(2.4.9) In a separating funnel, dissolve 1.0 g in 10 ml of In a separating funnel, dissolve 1.0 g in 10 ml of dilute hydrochloric acid Rdilute hydrochloric acid R. Shake with . Shake with

3 quantities, each of 10 ml, of 3 quantities, each of 10 ml, of methyl isobutyl ketone R1methyl isobutyl ketone R1, shaking for 3 min each time. , shaking for 3 min each time. To the combined organic layers add 10 ml of To the combined organic layers add 10 ml of water Rwater R and shake for 3 min. The and shake for 3 min. The aqueous layer complies with the limit test for iron (10 ppm). aqueous layer complies with the limit test for iron (10 ppm).

Heavy metals Heavy metals (2.4.8)(2.4.8) 2.0 g complies with limit test D for heavy metals (10 ppm). Prepare the standard using 2.0 g complies with limit test D for heavy metals (10 ppm). Prepare the standard using

2 ml of 2 ml of lead standard solution (10 ppm Pb) Rlead standard solution (10 ppm Pb) R. . Loss on drying Loss on drying (2.2.32)(2.2.32) Not more than 0.5 per cent, determined on 1.000 g by drying in an oven at 100-105 Not more than 0.5 per cent, determined on 1.000 g by drying in an oven at 100-105

°C. °C. Sulphated ash Sulphated ash (2.4.14)(2.4.14) Not more than 0.1 per cent, determined on 1.0 g.Not more than 0.1 per cent, determined on 1.0 g.

ASSAYASSAY Dissolve 0.130 g in 50 ml of Dissolve 0.130 g in 50 ml of carbon dioxide-free carbon dioxide-free

water Rwater R with gentle heating. Cool. Using 0.1 ml of with gentle heating. Cool. Using 0.1 ml of bromothymol blue solution R1bromothymol blue solution R1 as indicator, titrate as indicator, titrate with with 0.1 M sodium hydroxide0.1 M sodium hydroxide until the colour until the colour changes from yellow to blue. changes from yellow to blue.

1 ml of 1 ml of 0.1 M sodium hydroxide0.1 M sodium hydroxide is equivalent to is equivalent to

14.71 mg of C5H9NO4. 14.71 mg of C5H9NO4. STORAGESTORAGE Protected from light. Protected from light. Ph EurPh Eur

Glutamic acid hydrochlorideGlutamic acid hydrochloride (Acidulin)(Acidulin)

It is essentially a pure compound that occurs as a white crystalline It is essentially a pure compound that occurs as a white crystalline powder soluble 1:3 in water and insoluble in alcohol. It has been powder soluble 1:3 in water and insoluble in alcohol. It has been used in place of glycine in the treatment of muscular dystrophies, used in place of glycine in the treatment of muscular dystrophies, with rather unpromising results. It also is combined with with rather unpromising results. It also is combined with anticonvulsants for the petit small attacks of epilepsy, a use that anticonvulsants for the petit small attacks of epilepsy, a use that appears to depend on change in pH of the urine.appears to depend on change in pH of the urine.

IdentificationIdentification. . A. A. As all amino acids glutamic acid reacts with As all amino acids glutamic acid reacts with ningidrin:ningidrin:

*

O

O

O

H2O

COOH

CH NH2

R

+ CH

O

O

OH CHO

R+ NH3 CO2+ +

O

O

O

NH H H+ +

O

O

HOH2O

O

N

O O

HO

NH3

O

N

O O

ONH4

blue-violet

B.B. Amino acids react with copper salts to form blue-violet Amino acids react with copper salts to form blue-violet complexes:complexes:

HOOC CH2 CH2 CH COOH

NH2

CuSO4 NaOH2+ +

CuO

O

CC

CH

CH

NH2

O

O

H2NCH2 CH2

CH2CH2

COOH

HOOC+ +Na2SO4 2H2O

2

C. Glutamic acid reacts with resorcin in presence of H2SO4k.

HOOC CH2 CH2 CH COOH

NH2

t*H2O

NH

O

COOH

+ 2

OHHO

HO O OH

NH

COOH

H2SO4

H2O2

NH4OH

HO O OH

COONH4

OHNH2

HO O O

COONH4NH2

H2O

red-violet

red

AssayAssay Alkalimetry, direct titrationAlkalimetry, direct titration. .

(neutralization titration) (using NaOH (neutralization titration) (using NaOH as titrant; bromthymole blue as as titrant; bromthymole blue as indicator).indicator).

Еm(C5H9NO4) = М.m.Еm(C5H9NO4) = М.m.

AcetylcysteineAcetylcysteine (Mucomyst) (Mucomyst) Is the N-acetyl derivative of L-cysteine. It is used Is the N-acetyl derivative of L-cysteine. It is used

primarily to reduce the viscosity of the abnormally primarily to reduce the viscosity of the abnormally viscid pulmonary secretions in patients with cystic viscid pulmonary secretions in patients with cystic fibrosis of the pancreas or various fibrosis of the pancreas or various tracheobronchial and bronchopulmonary diseases.tracheobronchial and bronchopulmonary diseases.

Acetylcysteine is more active than cysteine. Acetylcysteine is more active than cysteine. Acetylcysteine is most effective in 10% to 20% Acetylcysteine is most effective in 10% to 20% solutions. It is used by direct instillation or by solutions. It is used by direct instillation or by aerosol nebulization. It is available as a 20% aerosol nebulization. It is available as a 20% solution of the sodium salt in 10- and 30ml solution of the sodium salt in 10- and 30ml containers. An opened vial of acetylcysteine must containers. An opened vial of acetylcysteine must be covered, stored in a refrigerator, and used be covered, stored in a refrigerator, and used within 48 houts.within 48 houts.

MethionineMethionine (Amurex)(Amurex) MethioninumMethioninum ММETHIONINEETHIONINE

M. m. = 149,2 g/molM. m. = 149,2 g/mol С5H11NO2S С5H11NO2S

The chemical nameThe chemical name::-amino - -amino - --метилтиомаслянаяметилтиомасляная acid; acid; 2-2-4 (2-2-4 (метилтиометилтио) ) бутановаябутановая acid. acid.

DL-2-amino-4-(methylthio)-butyric acid DL-2-amino-4-(methylthio)-butyric acid (CH3SCH2CH2CH(NH2)COOH) occurs as white crystalline (CH3SCH2CH2CH(NH2)COOH) occurs as white crystalline platelets or powder with a slight, characteristic odor; it is platelets or powder with a slight, characteristic odor; it is soluble in water (1:30), and a 1% solution has a pH of 5.6 to soluble in water (1:30), and a 1% solution has a pH of 5.6 to 6.1. It is insoluble in alcohol. 6.1. It is insoluble in alcohol.

In therapy, methionine has been employed in the treatment In therapy, methionine has been employed in the treatment of liver injuries caused by poisons such as carbon of liver injuries caused by poisons such as carbon tetrachloride, chloroform, arsenic and trinitrotoluene. tetrachloride, chloroform, arsenic and trinitrotoluene. Methionin also has a function in the syntethis of choline, Methionin also has a function in the syntethis of choline, cystine, lecytin and probably creatine. Deficiency not only cystine, lecytin and probably creatine. Deficiency not only limits growth in rats, but also inhibits progression of tumors.limits growth in rats, but also inhibits progression of tumors.

AminalonumAminalonum Acidum gamma-aminobutyricumAcidum gamma-aminobutyricum Gamma bosoms Gamma bosoms HH2N-CH2–CH2–CH2–COOH2N-CH2–CH2–CH2–COOH Gammalonum Gammalonum

M. m. = 103,12 g/mol M. m. = 103,12 g/mol

C4H9NO2C4H9NO2 The chemical name: The chemical name: 4-aminobutyric acid, 4-aminobutyric acid, --

aminobytyric acid.aminobytyric acid.

ObtainingObtaining Alkaline hydrolysis pirolidone-2 Alkaline hydrolysis pirolidone-2 with the subsequent with the subsequent

neutralisation of salt of neutralisation of salt of -aminobytyric acid by means of -aminobytyric acid by means of acetic acid acetic acid СНСН33СООНСООН..

PropertiesProperties Description. Description. A white crystal powder with specific smell of A white crystal powder with specific smell of

amino acids. Hygroscopic.amino acids. Hygroscopic. SolubilitySolubility. Freely soluble in water, very slightly soluble in . Freely soluble in water, very slightly soluble in

alcohol, it is practically insoluble in chloroform, acetone. alcohol, it is practically insoluble in chloroform, acetone. рНрН a water solution 6,5 – 7,5a water solution 6,5 – 7,5..

IdentificationIdentification 1. Ninhydrin reaction1. Ninhydrin reaction; there is ; there is a blue-a blue-

violet violet colouring.colouring. 2. Reaction with alkaline solution 2. Reaction with alkaline solution

CuSO4CuSO4; it is formed chelate compound ; it is formed chelate compound of of intensively dark blue colour.intensively dark blue colour.

3. Fusion with KSCN3. Fusion with KSCN; allocation of; allocation of hydrogen sulphidehydrogen sulphide H H22S which revealing by S which revealing by means of lead-acetic papermeans of lead-acetic paper: :

S2 - + Pb2 + S2 - + Pb2 + PbS PbS blackblack 4. Heating with alloxan (mesoxalyl 4. Heating with alloxan (mesoxalyl

urea) in the medium of urea) in the medium of dimethylformamidedimethylformamide; there is a; there is a bright- bright-crimsoncrimson colouring. colouring.

AssayAssay 1. Acidimetry, non-aqueous 1. Acidimetry, non-aqueous

titration. titration. ТТitrant – itrant – perchlorate acidperchlorate acid HClO4, medium – HClO4, medium – anhydrous acetic anhydrous acetic acidacid СНСН33СООНСООН, the indicator – , the indicator – crystal crystal violetviolet (from (from violetviolet before before blue-greenblue-green colouring).colouring).

HOOC–(CH2)3–NH2 + HClO4 HOOC–(CH2)3–NH2 + HClO4 HOOC–(CH2)3–NH3+ClO4–HOOC–(CH2)3–NH3+ClO4–

In parallel spend In parallel spend control experience.control experience. ЕЕm (C4H9NO2) = M. m.m (C4H9NO2) = M. m.

2. Alkalimetry, direct titration of an investigated solution of a substance

by a standard solution NaOH in the presence of

the solution indicator bromthymol dark blue before transition of yellow colouring in the

blue-green.H2N - (CH2)3COOH + NaOH = H2N -

(CH2)3COONa + H2OЕm (C4H9NO2) = M. m.

StorageIn densely corked containers, in the dry cool

place protected from light.Application. Neuromediator

The release form: tablets on 0,25 g.

Aminocaproic acid Aminocaproic acid (Amicar)(Amicar) 6-Aminohexanoic acid occurs as fine, white 6-Aminohexanoic acid occurs as fine, white

crystalline powder that is freealy soluble in crystalline powder that is freealy soluble in water, slightly soluble in alcohol, and water, slightly soluble in alcohol, and practically insoluble in chloroform.practically insoluble in chloroform.

Aminocaproic acid has been used in the Aminocaproic acid has been used in the control of hemorrhage in certain surgical control of hemorrhage in certain surgical procedures. It is of no value in controlling procedures. It is of no value in controlling hemorrhage caused by thrombocytopenia hemorrhage caused by thrombocytopenia or other coagulation defects or vascular or other coagulation defects or vascular disruption. Aminocaproic acid is well disruption. Aminocaproic acid is well absorbed orally. Plasma peaks occur in absorbed orally. Plasma peaks occur in about two hours. It is rapidly, largely about two hours. It is rapidly, largely unchanged.unchanged.

CYSTEINE CYSTEINE CysteinumCysteinum

MM. m. = 121,2 g/mol. m. = 121,2 g/mol C3H7NO2C3H7NO2SS

Cysteine contains not less Cysteine contains not less than 98,0 %than 98,0 % and no and no more more than 101,0 %than 101,0 % (R)-2-amino-3- (R)-2-amino-3-mercaptopropanoic acid, in recalculation on a mercaptopropanoic acid, in recalculation on a solid.solid.

The chemical nameThe chemical name: (R)-2-amino-3-: (R)-2-amino-3-mercaptopropanoic acid.mercaptopropanoic acid.

PropertiesProperties Description. Description. A crystal powder of white colour A crystal powder of white colour

or colourless crystals with a characteristic smell.or colourless crystals with a characteristic smell. Solubility. Solubility. Freely soluble Freely soluble in water Rin water R and and 96 % 96 %

alcohol Ralcohol R, it is practically insoluble in ether, it is practically insoluble in ether R. R.

IdentificationIdentification The first identificationThe first identification: : AA, , B.B. The second identificationThe second identification: : AA, , B,B, C, D.C, D. A. Measuring of specific optical rotation by A. Measuring of specific optical rotation by

means method of polarimetrymeans method of polarimetry. From . From + 8,0to + 8,0to to + 9,5to + 9,5 in recalculation on a solid. Definition make, in recalculation on a solid. Definition make, using a substance solution in a solution 220 g/l using a substance solution in a solution 220 g/l chloride chloride acid R.acid R.

B. IR-spectroscopy.B. IR-spectroscopy. C. Reaction with ninhydrin.C. Reaction with ninhydrin. TechniqueTechnique. About 10 mg of a substance dissolve in 2 . About 10 mg of a substance dissolve in 2

ml ml of water Rof water R, add , add 0,1 M solution HCl 0,1 M solution HCl to рН nearby to рН nearby 4,0, 0,5 ml of a solution 2,5 g/l ninhydrin 4,0, 0,5 ml of a solution 2,5 g/l ninhydrin RR, heat up , heat up on a water heater during 10 mines; there is on a water heater during 10 mines; there is a yellowa yellow or or yellowy-brownyellowy-brown colouring. The received solution colouring. The received solution cool to a room temperature, add drops from 1 ml to cool to a room temperature, add drops from 1 ml to 2 ml 2 ml of 0,1 M solution NAOHof 0,1 M solution NAOH; there is ; there is a red-violet a red-violet colouring.colouring.

D. Identification mercapto-group with the help D. Identification mercapto-group with the help sodium nitroprusside after heating with alkali sodium nitroprusside after heating with alkali solutionsolution..

TechniqueTechnique. About 5 mg of a substance dissolve in 5 . About 5 mg of a substance dissolve in 5 ml ml water R water R, add 2 ml , add 2 ml solution solution NaOHNaOH diluted R diluted R and and 0,2 ml 25 g/l 0,2 ml 25 g/l solutionsolution sodium nitroprusside sodium nitroprusside Na2Na2 [Fe[Fe (CN)(CN) 5NO], 5NO], РР; there is ; there is a a yellow yellow colouringcolouring which which during 2 mines during 2 mines passes inpasses in the red the red..

2H2HS–CH2–CH2–CH(NH2)–COOH + 4NaOH S–CH2–CH2–CH(NH2)–COOH + 4NaOH Na2SNa2S + + 2NH32NH3 + +

2HO–CH2–CH2–CH(OH)–COONa2HO–CH2–CH2–CH(OH)–COONa Na2SNa2S + Na2[Fe(CN)5NO] + Na2[Fe(CN)5NO] Na4[Fe(CN)5NOS] Na4[Fe(CN)5NOS] E.E. Reaction with H2O2 and solution FeCl3Reaction with H2O2 and solution FeCl3 and and

the next revealing SO42- by means of reagent the next revealing SO42- by means of reagent barium of chloride R1 in the medium of chloride acid barium of chloride R1 in the medium of chloride acid diluted R.diluted R.

SO42 - + Ba2 + SO42 - + Ba2 + BaSO4BaSO4white precipitate or white precipitate or opalescenseopalescense

Reaction with salts of CopperReaction with salts of Copper (ІІ); (ІІ); the blackthe black precipitate is formed.precipitate is formed.

TestsTests 1. рН solution. 1. рН solution. From From 4,54,5 to to 6,06,0.. 2. Specific optical rotation2. Specific optical rotation. From . From +8,0 +8,0

to +9,5,to +9,5, in recalculation on a solid. in recalculation on a solid. Measure optical rotation of solution Measure optical rotation of solution substance in 220g/l solution chloride substance in 220g/l solution chloride acid.acid.

3. The general impurity3. The general impurity of chlorides, of chlorides, sulphates, ammonium of salts, Iron, heavy sulphates, ammonium of salts, Iron, heavy metals – within corresponding standards.metals – within corresponding standards.

4. Weight loss at drying4. Weight loss at drying. At drying 1,000 . At drying 1,000 g substance at temperature from g substance at temperature from 100 100 CC to to 105 105 CC weight loss should be no more weight loss should be no more than than 0,5 %0,5 %..

9. Sulphatic ashes.9. Sulphatic ashes. No more No more than than 0,1 %0,1 %. Definition spend with 1,0 g . Definition spend with 1,0 g substance.substance.

10. Pyrogens or bacterial endotoxins.10. Pyrogens or bacterial endotoxins.

ASSAYASSAY 1. SPU. Iodometry, back titration1. SPU. Iodometry, back titration. Shot of substance . Shot of substance

dissolve in dissolve in НСНСl l diluted Rdiluted R, cool in an ice cooler, add , cool in an ice cooler, add crystal crystal КІКІ and excess and excess of a standard solution of a standard solution ІІ2. After keeping of a 2. After keeping of a solution during 15 mines in the place protected from light solution during 15 mines in the place protected from light not reacted not reacted ІІ2 titrate by2 titrate by standard solution standard solution Na2S2O3, using in Na2S2O3, using in the end of titration the the end of titration the indicator indicator starchstarch (before (before disappearancedisappearance of dark blueof dark blue colouring). colouring).

H2C

HC COOHHS

NH2

CHH2C COOH

NH2

S

SH2C

HC COOH

NH2

2 + I2 + 2HI Em=M.M

cysteine T homocystin

I2 + 2Na2S2O3 = 2NaI + Na2S4O6 not reactedIn parallel spend control experience.

Еm (C3H7NO2S) = M. m.

2. Iodometry, direct titration2. Iodometry, direct titration. . Shot of substanceShot of substance dissolve in dissolve in solution solution HCl, add KI and titrate byHCl, add KI and titrate by standard solution standard solution I2 in the I2 in the presence of presence of starchstarch before occurrence before occurrence of dark blueof dark blue colouring. colouring.

StorageStorage In densely corked containers, in banks from dark glass, in the In densely corked containers, in banks from dark glass, in the

place protected from light.place protected from light. Application. For treatment of initial forms of a cataract.Application. For treatment of initial forms of a cataract. Apply Apply 5 %5 % water solution at initial forms of a cataract. Is a part water solution at initial forms of a cataract. Is a part

of eye drops.of eye drops.

H2C

HC COOHHS

NH2

CHH2C COOH

NH2

S

SH2C

HC COOH

NH2

2 + I2 + 2HI Em=M.M

Thanks for attention!