Chapter 6. Drug analysis of alicyclic carboxylic acids, hydroxy acids, ascorbic acid, aliphatic amino acids and their derivatives

INTRODUCTION

Alicyclic acids (lactic, pyruvic, citric, acetic acid) play a significant role in the activity of the living organism. In this regard, the pharmaceutical use of salts of these acids is biologically related for the human body due to the same anion administration, although the action of these drugs is based on their cation part.

Ascorbic acid (a vitamin drug) that is studied in this chapter is the lactone of the unsaturated hydroxy acid. It exhibits acid properties through the presence of enolic hydroxyl groups in the molecule.

Amino acids are vital for any living organism, that is why they are widely used as drugs involved in the nitrogen metabolism and nervous system functioning.

Salts of alicyclic carboxylic acids

Formulae and properties of drugs that form a group of alicyclic carboxylic acid salts are presented in the Table 6.1.

Table 6.1. Alicyclic carboxylic acid salts

Compound name (INN, English, Latin) Chemical structure	Physical and chemical properties Application
Potassium acetate Kalii acetas CH3COOK C2H3K02 M.m. 98.15	White crystalline powder, odorless or with a faint acetic odor; very soluble in water
Calcium lactate Calciil acetas С6Н10СаО6 · 5Н20 M.m.308.30	White fine powder, almost odorless; efflorescent in air; soluble in water (slowly), easily soluble in hot water
Calcium gluconate Calcii gluconas С12Н22СаО14 · Н2О M.m. 448.4	White granular or crystalline powder, odorless; freely soluble in boiling water, sparingly (slowly) soluble in water, practically insoluble in 96 percent alcohol
Sodium citrate dihydrate Natrii citras dihydricus C6H5O7Na3 · 2Н2О M.m. 294.10	White or almost white crystalline powder or white or almost white granular crystals; efflorescent in air; soluble in water, practically insoluble in ethanol

Identification

Acetate-ion:

• Reaction with iron (III) chloride:

• Reaction of ethyl acetate formation that has a characteristic odor:

Citrate-ion: reaction with calcium chloride solution:

The precipitate is formed only when boiling. At room temperature calcium citrate is soluble in water.

Gluconate-ion: reaction with iron (III) chloride. The presence of several hydroxy groups and carboxy group enables the formation of light-green salt with FeCl₃. The salt is soluble in water. Calcium gluconate identification involves IR spectrum obtaining.

Lactate-ion: there is a hydroxy acid oxidation ability with different product formation. Lactate-ion oxidation by potassium permanganate results in acetaldehyde formation, that is detected by its characteristic odor:

Lactate oxidation by iodine in alkaline medium results in iodoform formation that has a characteristic color and odor:

Sodium, potassium and calcium cations are identified by general identification reactions of ions as required the current edition of the State Pharmacopoeia of the Russian Federation.

Sodium ion:

• yellow flame color;
• reaction with potassium pyroantimonate.

Potassium ion:

• purple flame color;
• reaction with tartaric acid.

Calcium ion:

• red-orange flame color;
• reaction with ammonium oxalate.

Assay

Acidimetry in aqueous medium

This method is based on strong mineral acid ability to displace organic acid from its salt.

Tropeolin 00 is utilized as indicator in potassium acetate determination. The releasing acetic acid does not change tropeolin 00 color, but the excessive drop of hydrochloric acid does:

CH₃COOK + HCl → CH₃COOH + KCl

Assay of sodium citrate is carried out by hydrochloric acid titration:

Diethyl ether is added to the reaction mixture.

Acid-base nonaqueous titration

Nonaqueous solvent - glacial acetic acid; titrant - 0.1M perchloric acid solution; indicator - crystal violet.

Potassium acetate is dissolved in glacial acetic acid:

CH₃COOK + CH₃COOH → CH₃COOKH⁺ ∙ CH₃COO^-

HClO₄+CH₃COOH → ClO₄⁻ ∙ CH₃COOH₂⁺

CH₃COOKH⁺ ∙ CH₃COO⁻ + ClO₄⁻ ∙ CH₃COOH₂⁺ → KClO₄ + 3CH₃COOH

sodium citrate injection solution is determined under the same conditions.

Complexometric titration

Calcium ion is determined by complexometric titration in calcium lactate and calcium gluconate (see p. 77).

Ascorbic acid

Vitamin C is found in organs of many crops and wild plants. Ascorbic acid is a γ-lactone, that contains 2 alcohol hydroxyl groups in 5 and 6 positions and 2 enolic hydroxyl groups in 2 and 3 positions.

Physical properties

Ascorbic acid is a white crystalline powder with a sour taste, freely soluble in water. It contains 2 asymmetric carbon atoms. Ascorbic acid is optically active. Physical and chemical properties of ascorbic acid are presented in the Table 6.2.