Inorganic Chemistry: Prep & Assay

• The presentation covers pharmaceutical inorganic chemistry, focusing on the preparation and assay of various compounds
• Students should be able to describe the preparation, assay, and uses of the compounds discussed

Compounds Covered

• Sodium Chloride
• Calcium Gluconate
• Ammonium Chloride
• Sodium Bicarbonate
• Hydrogen Peroxide
• Chlorinated Lime
• Ferrous Sulphate
• Sodium Thiosulphate
• Copper Sulphate

Sodium Chloride

• Has a molecular weight of 58.44 g/mol
• Prepared by evaporating sea water in shallow pans on a commercial scale
• Often contains impurities like sodium carbonate, sodium sulphate, magnesium chloride, magnesium sulphate, and calcium chloride
• Impurities can be removed by dissolving alum (hydrated double sulfate salt of aluminum with the general formula KAl(SO₄)₂·12 H₂O) in water in cemented tanks
• Suspended impurities settle down, then the clear solution is decanted into iron pans and concentrated before the sodium chloride crystals are dried
• Contains not less than 99.5% and not more than 100.5% NaCl calculated with reference to dried substance, with no added substances
• Exists as colorless cubic crystals or white crystalline powder with a saline taste
• Freely soluble in water, more soluble in boiling water, soluble in glycerine, and slightly soluble in alcohol
• A 0.9% aqueous solution is iso-osmotic
• Should be stored in a well-closed container

Sodium Chloride: Purity Tests and Assay

• Must be tested for acidity and alkalinity, arsenic, iron, heavy metals, potassium, calcium, magnesium, loss on drying, clarity, and color of the solution
• Assay is determined by Modified Volhard's method

Sodium Chloride: Uses

• Electrolyte replenisher
• In the manufacture of isotonic solutions
• Flavor enhancer
• Isotonic solutions are used in wet dressings for irrigating body cavities or tissues
• Hypotonic solutions, with a lower solute concentration than intracellular fluids, are used for maintenance therapy in patients unable to take fluids and nutrients orally for one to three days
• Hypertonic solutions, with a higher solute concentration than intracellular fluids, or injections are used when there is a loss of sodium in excess
• A 0.9% solution is used as eye drops, nasal drops, and as a mouthwash
• Used in dermatological preparations as a hydrating agent

Calcium Gluconate

• An anhydrous compound
• Can be used as a mineral supplement and essential body electrolyte
• Supports muscle and nerve integrity
• Essential for muscle contraction, cardiac functions, and blood coagulation
• Synonyms include Calcium D-gluconate, Calcium salt of Gluconic acid, Gluconic Acid hemi-calcium salt
• Chemical formula: C₁₂H₂₂CaO₁₄
• Slowly soluble in water, insoluble in organic solvents and alcohol
• It is inorganic and mildly acidic
• Exists as a powder or granules
• Odorless

Calcium Gluconate: Assay

• Weigh approximately 0.5 g of the dried sample
• Dissolve in 5 ml of dilute hydrochloric acid
• Add 50 ml of water, 25 ml of sodium hydroxide, and about 0.1 g of calconcarboxylic acid, Patton-Reeder indicator
• Titrate with 0.05 M EDTA immediately, the red color will change to blue at the end-point
• Plays a role in the physiology of the organism and cell
• Pivotal in signal transduction pathways
• Acts as a 2nd messenger in neurotransmitter release of neurons and contraction of all muscle cell types
• Extracellular calcium is important for maintaining potential difference across excitable cell membranes and bone formation
• Absorbed from the small intestine via active transport and passive diffusion
• It crosses the placenta and enters breast milk

Calcium Gluconate: Therapeutic Uses and Drug Interactions

• Used to treat hypocalcemia, including hypoparathyroidism, magnesium sulphate overdose and hydrofluoric acid burns
• It reacts with hydrofluoric acid to form insoluble, nontoxic calcium fluoride
• Should not be taken with digoxin, antacids or calcium supplements, Vitamin-D supplements, or antibiotics like doxycycline and tetracycline

Sodium Bicarbonate

• Baking soda with the formula NaHCO₃
• Has a molecular weight of 84.01 g/mol
• Acts as a weak, short-acting antacid
• Prepared by saturating strong brine (a solution of water with usually sodium chloride or calcium chloride) containing high concentrations of ammonia with carbon dioxide in a carbonating tower under pressure; the resulting ammonia bicarbonate is reacted with NaCl to precipitate NaHCO₃
• Also prepared by covering sodium carbonate crystals with water and saturating with carbon dioxide
• It is a white crystalline powder, odourless, with saline and slightly alkaline taste, is stable in dry air, sparingly soluble in water, and insoluble in alcohol

Sodium Bicarbonate: Identification and Assay

• Identification can be done on a 5% w/v solution in carbon dioxide free water with 0.1ml of phenolphthalein solution, which will result in a pale pink color; heating evolves a gas and turns the solution red
• Assay is performed by accurately weighing 1gm and dissolving in 20ml of water, then titrating with 0.5N sulphuric acid using methyl orange as the indicator
• Used as an antacid and in electrolyte replacement

Hydrogen Peroxide

• Chemical formula is H₂O₂
• Oxygenated water

Hydrogen Peroxide: Properties and Preparation

• Hydrogen peroxide solution is available in (100 Vol) (27% w/v) and (20 Vol) (6% w/v)
• Acts as an oxidant, producing hydroxyl free radicals (OH) that attack essential cell components like lipids, proteins, and DNA
• Molecular weight: 34.02 g/mol
• Pure (100%) hydrogen peroxide is an unstable, colorless, syrupy liquid
• Boils at 63° C, decomposes with explosive violence at 100° C, forming water and oxygen
• It is converted to transparent crystals when cooled at 10° C, and is miscible with water and alcohol
• Structural formula: H-O-O-H, the oxygen-oxygen bond is very weak
• Various substances in minute amounts can cause the decomposition of hydrogen peroxide
• Is stabilized by acidic stabilizers (inorganic or organic acids), complex forming stabilizers (acetanilide, phenacetin, quinine sulphate and 8-hydroxyquinolines), and adsorptive stabilizers (alumina, silica, hydrous antimony oxide and stannic oxide); these stabilizers minimize decomposition

Hydrogen Peroxide: Chemical Properties and Commercial Manufacture

• Hydrogen peroxide is very slightly ionized in water
• Undergoes exothermic decomposition with the following reaction: 2H₂O₂ → 2H₂O + O₂ (46,200 cal)
• Acts as an active oxidizing agent
• Can be manufactured with non electrolytic methods using the reactions: BaO₂·2H₂O + H₂SO₄ → BaSO₄ + H₂O₂ + 8H₂O or Na₂O₂ + H₂SO₄ → H₂O₂ + Na₂SO₄
• Electrolytic method: By the electrolysis of sulphuric acid, 2H₂SO₄ → H₂S₂O₈ + H₂ (peroxy disulphuric acid)
• H₂S₂O₈ + H₂O → H₂SO₅ + H₂SO₄ (peroxy sulphuric acid)
• H₂SO₅ + H₂O → H₂O₂ + H₂SO₄

Hydrogen Peroxide: Assay, Physiological Properties, and Uses

• Assay using Permanganate Titration
• Method utilizes the reduction of potassium permanganate (KMnO₄) by hydrogen peroxide in sulfuric acid
• Even a 3% solution should be avoided internally because sufficient irritation can cause bleeding and decomposition with the evolution of much oxygen, which can be dangerous
• Vapors are an irritant, causing the skin to whiten
• Used as an antiseptic due to the liberation of atomic oxygen when in contact with tissues, blood, and pus
• It kills the most pathogenic microorganisms
• Used to loosen ear wax
• Undiluted solutions may be used as a mouth wash several times daily in treating "Vincent's stomatitis“ and caries

Ammonium Chloride

• Has an alternative name of Salt armoniack and the formula NH₄Cl
• Prepared by the neutralization of hydrochloric acid with ammonia, followed by evaporating to dryness and purifying through recrystallization
• Neutralization process: NH₃ + HCl → NH₄Cl
• Exists as a colorless or white crystalline powder, odorless and saline in taste, hygroscopic
• Soluble in water and glycerol

Ammonium Chloride: Assay

• Involves indirect acid base titrations
• Substance solution is mixed with neutral formaldehyde leading to the liberation of HCl from NH₄Cl
• Titrated with 0. 1 N NaOH, using phenolphthalein as the indicator, and the end point will be show a pink color
• 4NH₄Cl + 6HCHO → (CH₂)₆N₄ + 4HCl + 6H₂O
• Method involving solution of the substance (acidified with HNO₃) and shaken with a measured volume of N/10 silver nitrate: AgNO₃ + NH₄Cl → AgCl + NH₄NO₃, and excess silver nitrate determined by titration with N/10 ammonium thiocyanate using ferric ammonium sulphate as indicator
• It should stored in a well closed air tight container
• Used as an expectorant and diuretic
• Used to treat severe metabolic alkalosis
• Uses to maintain urine at an acid pH, treatment of urinary tract disorders

Chlorinated Lime

• With the formula [Ca(OCl)Cl]
• Also called Bleaching Powder and Calcium chlorohypochlorite
• Contains not less than 30% w/w of available chlorine
• Should be Stored in tightly stoppered container
• Slaked lime (Calcium hydroxide) is treated with chlorine gas, the temperature is maintained below 25°C, absorption of chlorine can take 12 to 24h
• Reaction: Ca(OH)₂ + Cl₂ = Ca(OCl)Cl + H₂O
• White granular powder with the odor of chlorine and decomposes when exposed to air

Chlorinated Lime: Assay and Use

• Involves an aqueous suspension of the substances being treated with excess of potassium iodide and acetic acid
• The liberated chlorine displaces an equivalent amount of iodine from potassium iodide
• The iodine that is produced is then titrated against 0. 1N sodium thiosulphate using starch mucilage as indicator
• Used as a bleaching agent and disinfectant

Ferrous Sulphate

• Has the formula FeSO₄·7H₂O with a molecular weight of 278.03 g/mol
• In moist air, the crystals rapidly oxidize to a brownish-yellow, colored salt called "basic ferric sulphate"
• Sparingly soluble in water
• Combines with the alkali sulphates to form double salts, ferrous ammonium sulphate FeSO₄·(NH₄)₂SO₄·6H₂O (mohr's salt)
• Undergoes oxidation to ferric sulphate: 10FeSO₄ + 2KMnO₄ + 8H₂SO₄ → 5Fe₂(SO₄)₃ + 2MnSO₄ + K₂SO₄ + 8H₂O
• Manufactured with Fe + H₂SO₄ → FeSO₄ + H₂, 2FeS₂ + 7O₂ + 2H₂O → 2FeSO₄ + 2H₂SO₄
• An efficient haematinic
• It May cause gastric discomfort
• Exiccated ferrous sulphate” is (Dried ferrous sulphate)

Ferrous Sulphate: Assay

• Dissolve about 1 g of the sample, accurately weighed, in a mixture of 25 ml of 2 N sulfuric acid and 25 ml of recently boiled and cooled water, add orthophenanthroline, and immediately titrate with 0. 1 N cerric sulfate

Sodium Thiosulphate

• Formula: Na₂S₂O₃ · 5H₂O
• In the structure of sodium thiosulphates the sulphur is in two oxidation states
• One of the sulphur atom oxidised and resisted to further atom oxidation
• The other sulphur atom is in zero oxidation state, acting as a reducing agent or as an antioxidant
• Prepared by boiling sodium sulphite solution with S in absence of air, and filtrate is evaporated to give crystals of sodium thiosulphates with S removed
• Test for purity for arsenic, chloride, heavy metals, sulphide, sulphate and sulphite and clarity and colour of solution
• Add sodium nitroprusside solution to the aqueous solution of the sodium thiosulphate, and the solution does not become violet

Sodium Thiosulphate: Assay and Uses

• Dissolve about 800 mg of Sodium Thiosulfate, accurately weighed, in 30 mL of water and adjust by the addition of 3 N hydrochloric acid to a pH of between 6.2 and 6.7 and titrate with 0. 1 N iodine, adding 3 mL of starch as the endpoint is approached
• A reducing agent, in iodine titrations in volumetric analysis, antidote for cyanide poisoning when used with sodium nitrite, antidote in mercury, iodine, lead and bismuth and treats dermatological problems with acids

Copper Sulphate

• Formula: CuSO₄·5H₂O
• Molecular Weight: 249.69
• Called cupric sulphate, it occurs in the form of deep blue, triclinic crystals or as blue crystalline granules or powder, effloresces slowly in dry air
• Crystals become covered with a white coating, the salt is odourless and has a nauseous metallic taste, soluble in water and very insoluble in alcohol
• Chemical properties: On heating at 60° C, the crystal loses two water molecules (CuSO₄·3H₂O). At 140° C, another water molecule is lost (CuSO₄·2H₂O), and at 200° C, the white anhydrous salt is formed (CuSO₄)
• At higher temperature it is decomposed to sulphur dioxide, oxygen and cupric oxide: 2CuSO₄ → 2CuO + 2SO₂ + O₂
• Used extensively in the determination of reducing sugars in the form of "fehling's solution" and "benedict's solution“
• Fehling's solution includes solution A with copper sulphate solution and solution B with potassium and sodium tartrate

Formulations of Benedict's Solution

• Qualitative: includes crystalline copper sulphate, sodium citrate, and monohydrate sodium carbonate
• Quantitative: includes crystalline copper sulphate, sodium citrate, sodium carbonate, potassium thiocyanate and potassium ferrocyanide solutions

Copper Sulphate: Commercial Manufacture

• Includes 2Cu + 2H₂SO₄ + O₂ → 2CuSO₄ + 2H₂O and Cu + H₂SO₄ → CuO + SO₂ + H₂O with CuO + H₂SO₄ → CuSO₄ + H₂O (cooling) and CuSO₄ + 5H₂O → CuSO₄·5H₂O

Copper Sulphate: USES

• Stimulates vomiting reflex
• Not absorbed and hence produces no systemic effects
• Used to empty the stomach of indigestible food and poisons
• Externally used as fungicidal in athlete's foot
• As a weak bactericide in urethral injections
• Frequently small quantities are used with iron / vitamins for haemitinic property