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Authenticity reactions and methods for quantitative determination of drugs anesthesin and dicaine hydrochloride. Dicain: instructions for use of eye drops Dicain quantitative determination

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Coursework

Topic: 2.4 "Authenticity reactions and methods for quantitative determination of drugs anesthesin and dicaine hydrochloride"

Introduction

1. Justification of authenticity reactions and methods of quantitative determination based on their properties of the aromatic amino group for organic compounds

2. Identification and quantification of anesthesin (benzocaine)

2.1 Authenticity reaction equations

2.2 Methods of quantitative determination. Content calculation

3. Identification and quantification of dicaine hydrochloride (tetracaine hydrochloride)

3.1Authenticity reaction equations

3.2 Methods of quantitative determination. Content calculation

Conclusion

References

Introduction

The course work is aimed at considering authenticity reactions and methods of quantitative determination in proposed medicines based on the properties of functional groups.

The purpose of the work is to consider theoretical issues of methods for determining the authenticity and quantitative determination of individual preparations containing an aromatic amino group on the basis of regulatory documentation, GF X and GF XII, FS.

Qualitative and quantitative analysis of organic drugs consists of reactions to the corresponding functional groups present in the compound. The course work presents the main qualitative reactions to functional groups, as well as methods for the quantitative determination of substances, determining numerical indicators for calculating quantitative content.

Performing a pharmacopoeial analysis makes it possible to establish the authenticity of the drug, its purity, and determine the quantitative content of the pharmacologically active substance or ingredients included in the dosage form. Although each of these stages has its own specific purpose, they cannot be considered in isolation. They are interconnected and mutually complement each other.

1. RationalereactionsauthenticityAndmethodsquantitativedefinitionsbased ontheirpropertiesaromaticamino groupsFororganicconnections

2. DefinitionauthenticityAndquantitativedefinitionsanesthesin (benzocaine)

2.1 Equationsreactionsauthenticity

aromatic amino group anesthesin benzocaine

A) General reactions of n-aminobenzoic acid esters having an unsubstituted primary aromatic amino group

Reaction of formation of azo dye. The diazotization reaction occurs under the influence of sodium nitrite in an acidic environment. As a result, unstable diazonium salts are formed. With the subsequent addition of an alkaline solution of any phenol (β-naphthol, resorcinol, etc.), a cherry, red or orange-red azo dye is formed.

WhereR-WITH 2 N 5

Anestesin forms a Schiff base when it reacts with aldehydes, for example with n-dimethylaminobenzaldehyde in the presence of concentrated sulfuric acid, a yellow or orange color appears:

WhereR-WITH 2 N 5

When interacting with hydroxylamine in an alkaline environment, benzocaine forms hydroxamic acid, since it is an ester:

WhereR-WITH 2 N 5

When acidified with hydrochloric acid and adding a solution of iron (III) chloride, iron hydroxamate is formed, which has a red-brown color:

When performing this reaction, it is necessary to strictly follow the procedure, since the results are noticeable at a certain pH value.

Primary aromatic amines enter into condensation reactions with 2, 4 - dinitrochlorobenzene, forming zwitterion compounds with a quinoid structure. A yellow-orange color appears after adding the reagent, sodium hydroxide solution and heating. The colored compound is extracted with chloroform after acidification with acetic acid.

WhereR-WITH 2 N 5

Under the influence of chloroform and an alcohol solution of sodium hydroxide, isonitriles are formed, which have a nauseating odor:

WhereR-WITH 2 N 5

The condensation products with hexamethylenetetramine in the presence of concentrated sulfuric acid exhibit weak violet fluorescence.

Can be identified by precipitation (general alkaloid) reagents (picric, phosphotungstic, phosphomolybdic acids, mercury (II) chloride and others.

Benzocaine forms dibromo or diiodo derivatives.

When exposed to a 5% solution of chloramine in an acidic environment, a red-orange colored product is formed.

With nitric acid in concentrated sulfuric acid, a yellow-green color appears, turning to red with the addition of water and sodium hydroxide.

When benzocaine is mixed in glacial acetic acid with lead (IV) oxide, a red color appears.

B) Partial reaction to benzocaine - hydrolysis in a solution of sodium hydroxide, the resulting ethyl alcohol can be detected by the reaction producing iodoform, a yellow precipitate with a characteristic odor:

The presence of an ethoxyl radical in benzocaine can be determined by the action of acetic and concentrated sulfuric acids - by the characteristic fruity odor:

2.2 Methodsquantitativedefinitions.Calculationcontent

A) For the quantitative determination of anesthesin FS, a nitritometric method is recommended, based on the formation of diazonium salt:

1) potentiometrically;

Iodine-starch paper is porous, ashless filter paper soaked in a solution of starch with potassium iodide and dried in a dark place. Titration is carried out until a drop of the titrated solution taken 1 minute after the equivalence point

addition of titrant will not immediately cause a blue color on a strip of starch iodine paper:

2 KI+ 2 NaNABOUT 2 + 4 HCl= I 2 + 2 NO+ 2 KCl+ 2 NaCl+ 2 H 2 O

I 2 + starch= bluecoloring

K stech =Z =1

Mm. =165.19 g

M(1/Z) = 165.19 g/mol

Formula for calculating quantitative content taking into account the control experiment:

B) Bromide-bromometric method, based on the formation of dibromo derivatives:

Excess bromine is determined iodometrically, the indicator is starch, titrate until it turns blue:

Br 2 + 2 KI= I 2 +2 KBr

I 2 + Na 2 S 2 O 3 = 2 NaI+ Na 2 S 4 O 6

K stoich =1/Z =1/4 (based on the number of bromine atoms participating in the reaction)

Mm. =165.19 g

M(1/Z) = 41.3 g/mol

Formula for calculating quantitative content:

3. DefinitionauthenticityAndquantitativedefinitionsdicainehydrochloride(tetracainehydrochloride)

3.1 Equationsreactionsauthenticity

A) General reactions of n-aminobenzoic acid esters having a substituted primary aromatic amino group

Secondary amines under the influence of sodium nitrite form nitroso compounds:

An azo dye can also be obtained by adding a weakly acidic solution of an aromatic amine to a diazonium salt.

These reactions form the basis of the nitritometric method for the analysis of aromatic amines.

Condensation reactions. Aromatic amines enter into condensation reactions with 2, 4-dinitrochlorobenzene, aldehydes and other substances. As a result of the interaction of amines with aldehydes, Schiff bases are formed - compounds colored yellow or orange-yellow.

WhereR-WITH 4 N 9

Halogenation reactions. Substitution occurs in the ortho and para positions relative to the amino group. As a result of the bromination reaction, white or yellow precipitates are formed and bromine water becomes discolored.

Oxidation reactions. Under the influence of various oxidizing agents, aromatic amines form indophenol dyes

Reaction to an aromatic nitro group.

When an alkali acts on a compound containing a nitro group, the color intensifies to yellow, yellow-orange or red as a result of the formation of an aci salt.

Tetracaine hydrochloride from solutions is precipitated by potassium iodide in the form of hydrogen iodide salt

Under the influence of ammonium isothiocyanate, tetracaine isothiocyanate precipitates, the melting point of which is 130-132 ° C

Tetracaine hydrochloride, when interacting with potassium iodate in a phosphoric acid medium upon heating, forms a violet-colored oxidation product with a light absorption maximum at 552 nm. The reaction is specific for qualitative and quantitative determination.

B) Particular reactions to tetracaine hydrochloride:

Tetracaine hydrochloride, after heating with concentrated nitric acid and adding to the remainder of the potassium hydroxide solution, acquires a blood-red color. The reaction is based on its nitration and the subsequent formation of a potassium soliorthoquinoid compound:

For alkaline hydrolysis products:

Upon acidification, a white precipitate of p-butylaminobenzoic acid precipitates, which dissolves in excess hydrochloric acid:

From p-butylaminobenzoic acid, under the action of sodium nitrite, a precipitate of the N-nitroso compound of this acid precipitates:

Chloride ion detection reaction:

3.2 Methodsquantitativedefinitions.Calculationcontent

1. Nitritometry.

The method is based on the reaction of diazotization of primary and secondary aromatic amines with sodium nitrite, which is used as a titrant. Titration is carried out in an acidic environment (hydrochloric acid), at a low temperature, to prevent the decomposition of nitrous acid and diazonium salt; Potassium bromide is used as a catalyst. The diazotization reaction takes place over time, so titration is carried out slowly.

The equivalence point can be fixed in three ways:

1) potentiometrically;

2) using internal indicators - tropeolin 00 (color transition from red to yellow), tropeolin 00 mixed with methylene blue (color transition from red-violet to blue), neutral red (color transition from red-violet to blue);

3) using external indicators, for example, iodine-starch paper.

Secondary aromatic amines form nitroso compounds with sodium nitrite:

K stech =Z =1

Mm. = 300.83 g

M(1/Z) = 300.83 g/mol

Formula for calculating quantitative content:

Tetracaine hydrochloride can be determined by the amount of bound hydrochloric acid by alkalimetry; titration is carried out in the presence of chloroform, which extracts the released base:

Chloride ion argentometry method:

Conclusion

The primary or secondary aromatic amino group is contained in derivatives of p-aminobenzoic acid (novocaine, anesthesin, dicain, sodium diclofenac and others).

The mutual influence of atoms in a molecule affects the properties of aromatic amines. The lone electron pair of the nitrogen atom of the primary aromatic amino group is involved in conjugation with the p-electron system of the benzene ring. As a result, a shift in electron density occurs, which leads to activation of the ortho and para positions in the aromatic ring and a decrease in the basicity of the nitrogen atom in the amino group. Thus, aromatic amines are weak bases.

Aromatic amines are characterized by reactions of azo dye formation, condensation, halogenation, and oxidation.

Listliterature

1. Belikov, V. G. Pharmaceutical chemistry: a textbook for pharmaceuticals. Universities. - M.: Higher School, 2003. - 697 p.

2. Pharmaceutical chemistry: Textbook / ed. A.P. Arzamastseva.-2nd ed., revised.- M.: GEOTAR - Medicine, 2008.- 640 p.

3. State Pharmacopoeia of the USSR: X edition. 1968

4. State Pharmacopoeia of the USSR: X1 edition. Issue 1.- M.: Medicine, 1987.-336 p.

5. State Pharmacopoeia of the USSR: X1 edition. Issue 2. M.: Medicine, 1986.-368 p.

6. Dudko, V.V., Tikhonova, L.A. Analysis of medicinal substances by functional groups: textbook / ed. E. A. Krasnova, M. S. Yusubova. - Tomsk: NTL, 2004. - 140 p.

7. Guide to laboratory classes in pharmaceutical chemistry: textbook / ed. A. P. Arzamastseva. - M.: Medicine, 2004. - 384 p.

8. Pharmaceutical chemistry: textbook for universities / ed. A. P. Arzamastseva. - M.: GEOTAR-Media, 2006. - 640 p.

9. Chekryshkina L.A. et al. Analysis of drugs by functional groups. Perm. 2012

10. Chekryshkina L.A. et al. Methods of titritometric analysis. Permian. 2012

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Synonyms

Amethocaine, Anethaine, Decicain, Felicain, Foncaine, Intercain, Medicain, Pantocain, Pontocaine hydrochloride, Rexocaine, Tetracaini hydrochloridum, Tetracaine hydrochloride.

Physical properties

White crystalline powder, odorless. Easily soluble in water (1:10), alcohol (1:6). The solutions are sterilized at +100 °C for 30 minutes; to stabilize the solutions, a solution of hydrochloric acid is added to pH 4.0 - 6.0.

Application

Dicaine is used only for superficial anesthesia. Instead of dicaine, it is preferable to use less toxic local anesthetics (lidocaine, pyromecaine, etc.).

In ophthalmic practice, it is used in the form of a 0.1% solution when measuring intraocular pressure (one drop 2 times with an interval of 1 - 2 minutes). Anesthesia usually develops within 1 - 2 minutes. When removing foreign bodies and surgical interventions, use 2 - 3 drops of 0.25 - 0.5 - 1% or 2% solution. After 1 - 2 minutes, pronounced anesthesia develops. It must be taken into account that solutions containing more than 2% dicaine can cause damage to the corneal epithelium and significant dilation of conjunctival vessels. Typically, for anesthesia during eye surgery, a 0.5% solution is sufficient. To lengthen and enhance the anesthetic effect, add 0.1% adrenaline solution (3 - 5 drops per 10 ml of dicaine). Dicaine is not used for keratitis.

In ophthalmological practice, when long-term anesthesia is necessary, eye films with dicaine (Membranulae orthalmicae cum Dicaino) are used. Each film contains 0.00075 g (0.75 mg) of dicaine. The films are based on a biosoluble polymer.

Dicaine is also used for superficial anesthesia in otorhinolaryngological practice during some surgical interventions (puncture of the maxillary sinus, removal of polyps, conchotomy, middle ear surgery). Due to the rapid absorption of Dicaine by the mucous membranes of the respiratory tract, great care should be taken when using it and careful monitoring the patient's condition. Children under 10 years of age are not anesthetized with Dicaine. In older children, use no more than 1 - 2 ml of 0.5 - 1% solution, in adults - up to 3 ml of 1% solution (sometimes 0.25 - 0.5% solution is sufficient) and only if absolutely necessary - 2% or 3% solution. To the dicaine solution (in the absence of contraindications to the use of vasoconstrictors), add 1 drop of a 0.1% solution of adrenaline hydrochloride per 1 - 2 ml of dicaine.

The highest doses of dicaine for adults for anesthesia of the upper respiratory tract are 0.09 g once (3 ml of 3% solution). Dicaine doses should not be exceeded to avoid severe toxic effects. The literature describes cases of deaths associated with overdose and improper use of dicaine. Dicaine is contraindicated in children under 10 years of age and in patients with a general serious condition.

Features of work

When working with Dicaine, instruments and syringes should not contain any alkali residues, since Dicaine precipitates in the presence of alkali.

Release forms

Powder and films for the eyes with dicaine (30 pieces in dispensing cases).

Wikimedia Foundation. 2010.

Synonyms:

See what "Dikain" is in other dictionaries:

- (Dicainum) 2 Dimethylaminoethyl ester para butylaminobenzoic acid hydrochloride. Synonyms: Amethocaine, Anethaine, Decicain, Felicain, Foncaine, Intercain, Medicain, Pantocain, Pontocaine hydrochloride, Rexocaine, Tetracaini... ...

DICAINE- Dicainum. Synonyms: amethocaine, intercaine, pantocaine. Properties. White or white with yellowish crystalline powder, odorless, bitter taste. It causes a feeling of numbness on the tongue. Soluble in water (1:10), easily soluble in alcohol (1:6) ... Domestic veterinary drugs

Noun, number of synonyms: 1 analgesic (48) ASIS Dictionary of Synonyms. V.N. Trishin. 2013… Dictionary of synonyms

A drug that has a strong local analgesic (anesthetic) effect (see Painkillers). Used in powders and solutions for superficial anesthesia in ophthalmological and otolaryngological... ...

DICAINE- (Dicainum; FH, list A), local anesthetic. White crystalline powder, odorless. Easily soluble in water and alcohol. It is superior in activity and toxicity to novocaine and cocaine. Used primarily for superficial anesthesia in... Veterinary encyclopedic dictionary

DICAINE (Dicainum) 2 Dimethylaminoethyl ester of para butylaminobenzoic acid hydrochloride. Synonyms: Amethocaine, Anethaine, Decicain, Felicain, Foncaine, Intercain, Medicain, Pantocain, Pontocaine hydrochloride, Rexocaine, Tetracaini... ... Dictionary of medicines

diakin- Dikain Khitan... A short dictionary of anagrams

- (synonymous with local anesthetics) drugs that suppress the excitability of sensory nerve endings and block the conduction of impulses along nerve fibers. In medical practice, A. m. are used, belonging to two... ... Medical encyclopedia

Secondary amine of the aliphatic series (CH3)2NH, a colorless gas with a strong unpleasant odor, which easily liquefies when cooled into a colorless liquid; melting point 92.2°C, tkp 6.9°C. D. soluble in water and organic solvents, with acids... ... Great Soviet Encyclopedia

I Novocaine blockade is a method of nonspecific therapy consisting in the introduction of a novocaine solution into the tissue. Novocaine relieves severe irritation in the pathological focus, turns off peripheral innervation, resulting in... ... Medical encyclopedia

add 30% NaOH and quantitatively distill off the released ammonia into the receiver.

1) UV spectral analysis: a 0.002% solution of osalmide in 0.1 M NaOH is used. λ max =310 nm and 335 nm

Storage- according to list B, in a dry place, in a well-closed container, protected from light.

Application- choleretic agent in tablets of 0.25 - 0.5 g, 3 times a day.

Derivatives of n-aminobenzoic acid.

PABA (Vitamin H 1) is an integral part of the folic acid molecule.

PABA esters are local anesthetics, substances that suppress the sensitivity (excitability) of nerve endings. PABA esters have successfully replaced the alkaloid cocaine by mimicking its pharmacophore (anesthetic) group.

In 1879, the Russian scientist V.K. Antren discovered the anesthetic properties of the cocaine alkaloid.

Cocaine is isolated from the Erythroxylon Coca plant. The active principle is benzoylecgonine methyl ester. Toxic, addictive, difficult to obtain.

It is important:

Grouping of the basic nitrogen atom,

An ester group with an aromatic ring.

PABA derivatives exhibit the greatest activity with the general formula:

R 1, R 2 – alkyl substituents; X = O, S, NH.

The anesthetic effect depends on:

The nature of the aromatic acid;

N (hydrocarbon chain length);

From the molecular weight of alkyl radicals R 1 and R 2.

A decrease in physiological activity occurs due to:

Hydrogenation of the aromatic cycle;

Introduction of an electron-withdrawing group (NO 2) into the aromatic ring;

Introduction of an isostructural radical into the alkyl part.

Preparations:

A: PABA esters

І. Benzocaine, Aethylis Aminobenzoas*

Anestezin, Anaesthesinum

Ethyl ester of PABA (para-aminobenzoic acid).

White crystalline powder, odorless, slightly bitter taste. T.pl. = 89-91.5°C. Very slightly soluble in water, easily soluble in alcohol, chloroform, and ether. A weak base, its salts are fragile and quickly hydrolyze.

II. Novocaine, Novocainum,

Procaine hydrochloride, Procaini Hydrochloridum*

PABA β-diethylaminoethyl ester ( p- aminobenzoic acid) hydrochloride

White or white with a slightly creamy tint, odorless crystalline powder. T.pl. = 154 - 156˚С

Easily soluble in water and alcohol, slightly soluble in chloroform and ether.

III. Tetracaine hydrochloride, Tetracaini Hydrochloridum*

Dicainum Dicain.

β-diethylaminoethyl ether n- butylaminobenzoic acid hydrochloride

White crystalline powder, odorless. T.pl. = 147-150˚С. Easily soluble in water and alcohol, practically insoluble in ether.

B. PABA amide derivatives

IV. Procainamide hydrochloride

Procainamidi Hydrochloridum*

Novocainamidum Novocainamidum

β-diethylaminoethylamide PABA hydrochloride

White crystalline (sometimes with a creamy tint) odorless powder, m.p. = 165-169˚С. Very soluble in water, easily soluble in alcohol, slightly soluble in chloroform, practically insoluble in ether.

V. Metoclopamide hydrochloride, Metochlopamide*

4-amino-5-chloro–N–(2-(diethylamino)ethyl)–2-methoxybenzamide hydrochloride

White powder, easily soluble in water and alcohol.

B. Diethylaminoacetanilides.

VI. Trimecaine hydrochloride

Trimecainum, Trimecaini Hydrochloridum*

α-Diethylamino-2,4,6-trimethylacetanilide hydrochloride.

White or white with a slightly yellowish tint crystalline powder, very easily soluble in water, alcohol, chloroform, insoluble in ether.

Melting point = 139-142˚С.

VII. Lidocaine hydrochloride Lidocaini hydrochloridum

Xycain, Xycainum

α-Diethylamino-2,6-trimethylacetanilide hydrochloride.

White crystalline powder. Very soluble in water, soluble in alcohol, chloroform, insoluble in ether, bitter in taste.

T.pl. = 128-129˚С.

D. Local anesthetics similar in structure

VIII. Bupivacaine, Bupivacainum

Bupivacaine hydrochloride. Bupivacaini Hydrochloridum*

1-Butyl-N–(2,6–dimethylphenyl)–2-piperidinecarboxamide hydrochloride, monohydrate.

White crystalline powder, easily soluble in water.

IX. Ultracaine. Ultracainum.

Articaine hydrochloride. Articaini Hydrochloridum.

White powder, easily soluble in water.

Synthesis of PABA esters

The starting material is nitrobenzoic acid, which is obtained by the oxidation of n-nitrotoluene:

1) anesthesin (benzocaine), 1890

PABA ethyl ester (anesthetic)

2) procaine hydrochloride (Novocaine), 1905

→ novocaine

3) dicaine (tetracaine hydrochloride)

→ dicaine

Synthesis of PABA amides

The azo dye is cherry-red in color, and for anesthesin it is orange.

1.2. condensation reaction with aldehydes

(n- dimethylaminobenzaldehyde, furfural, vanillin)

1.3. condensation reaction with 2,4-dinitrochlorobenzene to form quinoid zwitter ions.

1.4. Color oxidation reactions (Cl 2, KMnO 4 in the presence of H 2 SO 4) to quinone imines.

2. Halogenation (bromination) reaction for anesthesin (GF X):

3. Reactions by ester and amide group (anesthesin, novocaine, novocainamide, dicaine, metoclopramide hydrochloride, trimecaine, lidocaine, bupivacaine, ultracaine).

3.1. proven by hydrolysis products (particular reactions)

A) alkaline hydrolysis (anesthesin)

Iodoform test

C 2 H 5 OH + 4 I 2 + 6NaOH = CHI 3 ↓ + HCOONa + 5NaI +5 H 2 O

B) acid hydrolysis

Identity is determined by reactions to primary amine (diazotization and formation of azo dyes).

C) after hydrolysis, the free base is isolated, the melting point of which is determined. In the filtrate after acidification with nitric acid, chlorine ions with silver nitrate are determined.

3.2. hydroxamic reaction

4. Reactions of a tertiary nitrogen atom or a quaternary ammonium base

4.1 due to the reaction of displacement of a base from its salt

4.2 acid-base interaction with the formation of complex compounds of the ionic type (bupivacaine, metoclopramide, dicaine, procainamide)

1. Reactions of the secondary amino group.

A specific reaction to dicaine is the Vitali-Morena reaction - nitration with the formation of acisols: dicaine is moistened with nitric acid, evaporated in a water bath, after cooling, an alcohol solution of KOH is added to the precipitate - a bright red color is obtained.

2. Reaction to covalently bound chlorine (metoclopramide)

3. Reaction to covalently bound sulfur (ultracaine)

4. IR and UV characteristics, mp.

5. Positive reaction to chlorine ion (hydrochlorides)

6. Color specific reactions:

trimecaine –

a) with copper acetate – green color

b) with H 2 O 2 +H 2 SO 4 conc. - blood red coloring

c) with Marki’s reagent – red coloring

d) microcrystalloscopic reaction of phenols with K 2 Cr 2 O 7 in the presence of concentrated H 2 SO 4 leads to the formation of crystals in the form of needles, grouped in the form of snowflakes.

lidocaine –

transferred to a base, dissolved in ethanol, tested for authenticity by reaction with cobalt chloride, resulting in a bluish-green precipitate.

anesthesin –

a) 5% chloramine in an acidic environment oxidizes to an orange product, which is extracted with ether.

b) in a medium of H 2 SO 4 and HNO 3, a yellow-green color is formed, turning into red after adding water and NaOH solution.

c) with ice CH 3 COOH and PbO 2 a red color is observed

novocaine

a) reaction with H 2 O 2 and concentrated H 2 SO 4 gives a lilac color

b) in the medium of H 2 SO 4 and HNO 3 an orange-red color is observed

procainamide

a) the reaction with K 4 Fe(CN) 6 + HCI gives a light green precipitate. By acting on the isolated base of the drug with benzoyl chloride, benzoylnovocainamide is obtained:

b) reaction with NH 4 NO 3 and H 2 SO 4 gives a cherry-red color

Dicaine

a) potassium iodide is precipitated from solution in the form of hydrogen iodide salt. Under the influence of ammonium isothiocyanate, dicaine isothiocyanate precipitates. T.pl. = 131 ˚С

b) with KI and H 3 PO 4 it forms a violet solution, for the oxidation product λ max = 552 nm.

Purity: control pH, clarity, presence or absence of general impurities.

Quantification

1. All PABA derivatives by GF are determined by the nitritometric method

a) primary amino group:

b) the secondary amino group (dicaine) is determined by the reaction of formation of nitroso compounds

The equivalence point is established using an external indicator (iodine-starch paper) and using an internal indicator: neutral red, tropeolin 00, a mixture of tropeolin 00 with methylene blue, potentiometrically.

2. For PABA hydrochloride derivatives, determination is carried out using hydrohalic acid.

2.1. neutralization method - alkalimetric titration

2.2. argentometric method (Faience version, medium – CH 3 COOH, indicator – bromophenol blue).

3. The iodochlorometric method (back titration option) is used for primary amines, titrant –ICl

ICl+KI → I 2 +KCl f eq =1/4

I 2 +2Na 2 S 2 O 3 → 2NaI+Na 2 S 4 O 6

4. The bromatometric method (anesthesin, novocaine) has limited use.

5. Acid-base titration in non-aqueous medium. The main advantage of the method is that it allows weak and very weak acids or bases to be titrated with reasonable accuracy.

5.1. Medium – anhydrous CH 3 COOH, crystal violet indicator, sometimes methyl orange.

The method of hydrolysis in a non-aqueous medium is based on the protonation of an organic base with a protogenic solvent and the ability of the latter to accept a proton from the titrant.

Peculiarity

For salts of an organic base, Hg(CH 3 COO) 2 is added to bind the halogen, while the halogen is converted to a low-ionized state and HCI does not affect the titration results.

Binding of an organic base halogen ion in the presence of Hg(CH 3 COO) 2:

2R + N(C 2 H 5) 2 HCl+2HClO 4 +Hg(CH 3 COO) 2 ®

®HgCl 2 +2RN(C 2 H 5) 2 HClO 4 +2CH 3 COOH

5.2. Titration in acetic anhydride in the absence of Hg(CH 3 COO) 2, but in acetic anhydride the binding of the halogen ion occurs according to the reaction:

Cl - + HClO 4 +(CH 3 CO) 2 O®

ClO - 4 + CH 3 COOH+CH 3 COCl

mechanism

Cl - + ClO 4 - → ClO 4 - + Cl -

The method is unified; the determination is carried out using the physiological part of the molecule. Can be used for water-insoluble substances and very weak bases.

6) spectrophotometric methods

a) in the UV region

λ max 292 nm (anesthesin) Sol-ethanol

285 nm 0.001 M HCI

298 nm (novocaine) Sol-water

290 nm Sol- 0.001 M HCI

280 nm (novocainamide) Sol-water

227 nm and 310 nm (dicaine) Sol - water

b) for novocaine – IR spectrum (MF).

c) in the visible region by color reactions. Reactions of azo dye formation with n- benzoquinone, Schiff bases, hydroxamic reaction.

d) extraction photocolorimetric method is based on obtaining a colored compound, extracting it in an organic solvent, and determining the optical density.

Acid dyes are used: methyl orange, bromophenol blue.

Storage: List B, dicaine – list A.

Drug, chemical formula	Class	Application	Release form	Note
Anestezin	ethers	Pain reliever, local anesthetic	Tablets, powders, external ointments, suppositories.	powders, “Menovazin”, “Amprovisol” tablets – 0.3 g.	Local anesthetic effect, antiarrhythmic effect, surgery, dentistry
Bupivacaine		Local anesthetic	Strong and long lasting. 3-10 hours or more ampoules and bottles 0.25% solution
Ultracaine		Anesthetic effect in dentistry	1% and 2% 1 ml each + adrenaline in dentistry, intramuscularly, subcutaneously

Molecular formula. Ci5H24N202-HC1.

Relative molecular weight. 300.8.

Structural formula.

CH3(CHg)3NH-Q-COOCH2CH2N(CH3)2

Chemical name. 2-(dimethylamino)ethyl p-(butylamino)ibenzoate monohydrochloride; 2-(dimethylamino)ethyl 4-(butylamino) benzoate monohydrochloride; per.

CAS No. 136-47-0.

Synonyms. Amethocaine hydrochloride; Dicaine

Description. White crystalline powder, odorless.

Solubility. Soluble in about 8 parts water; soluble in ethanol (- 750 g/l) TS; sparingly soluble in chloroform R; practically insoluble in ether R.

Storage. Tetracaine hydrochloride should be stored in a tightly closed container, protected from light.

Additional information. Tetracaine hydrochloride is hygroscopic; it has a slightly bitter taste and causes local numbness of the tongue. Even in the dark, it gradually decomposes in a humid atmosphere, and the destruction accelerates as the temperature rises.

Tetracaine hydrochloride melts at about 148°C or can occur in one of two polymorphic forms, one of which melts at 134°C and the other at 139°C. Mixtures of these forms melt in the range of 134-147 °C.

REQUIREMENTS

General requirement. Tetracaine hydrochloride contains at least

98.0 and not more than 101.0% Si5H24^02-HC1 in terms of the dried substance.

Authenticity

A. Dissolve 0.2 g of the test substance in 10 ml of water and add 1 ml of ammonium thiocyanate (75 g/l) TS. Collect the precipitate on a filter, recrystallize from water and dry for 2 hours at 80 °C; melting point is about 131 °C.

B. A solution of the test substance at a concentration of 20 mg/ml gives the characteristic reaction A for chlorides, described in the section “General tests for authenticity” (vol. 1, p. 129).

Transparency and color of the solution. A solution of 0.20 g of the test substance in 10 ml of carbon dioxide-free water R is clear and colorless.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 105 °C; loss no more than 10 mg/g.

pH of the solution. The pH of a solution of the test substance in carbon dioxide-free water P with a concentration of 10 mg/ml is 4.5-6.0.

Foreign impurities. Carry out the test as described in the section “Thin layer chromatography” (vol. 1, p. 92), using silica gel R4 as the sorbent, and a mixture of 80 volumes of dibutyl ether R, 16 volumes of hexane R and 4 volumes of glacial acetic acid as the mobile phase. acid R. Place the plate in the chromatographic chamber, immersing it 5 mm in the liquid. After the solvent front reaches a height of about 12 cm, remove the plate from the chamber and dry it for several minutes in a stream of warm air. Allow the plate to cool and apply separately 5 µl of each of 2 solutions containing (A) 0.10 g of the test substance in 1 ml and (B) 0.050 mg of 4-aminobenzoic acid R in 1 ml. Allow the solvent front to rise 10 cm above the application line. After removal from the chromatographic chamber, dry the plate for 10 minutes at 105 °C and evaluate the chromatogram in ultraviolet light (254 nm). Any stain produced by Solution A, other than the main stain, should not be more intense than the stain produced by Solution B. The main stain remains on the line of application.

Quantification. Carry out the test as described in the section “Nitritometry” (vol. 1, p. 153), using about 0.5 g of the test substance (accurately weighed) dissolved in a mixture of 50 ml of water and 5 ml of hydrochloric acid (-420 g / l ) TS, and titrate with sodium nitrite (0.1 mol/l) VS. Each milliliter of sodium nitrite solution (0.1 mol/l) VS corresponds to 30.08 mg of Ci5H24N202-HC1.