1

ESSENTIAL & TRACE ELEMENTS

CHAPTER NO-4

ESSENTIAL & TRACE ELEMENTS

2

Discussion about some important ions with their biochemical function but they are not important constituent of electrolyte powder or electrolyte replacement solutions. The important ions with their official compound likeIron Zinc Copper Manganese Selenium Sulphur & Iodine

A.IRON & ITS COMPOUNDS:

3

Used in form of its compounds asFerric salts (Fe+++) Ferrous salts (Fe++) Complex iron compounds as Ferric Amm. Citrate Iron is essential constituent of body & usual content- 45mg/kg body wt. Plays important role in body function. Essential constituent of blood system. Iron associated with diff. proteinsi.Hemoprotein ii.Iron storage protein iii.Iron transport protein

Responsible for respiration & for carrying oxygen. In the respiration Cytochrome-C is an enzyme in which iron is 4 complexed in porphirin(Heme) ring system which is covalently bonded to protein portion of molecule. porphirin (Heme) ring system of Cytochrome -C is differ from Hemoglobin in side chain. Other hemoprotein are myoglobin & hemoglobin which stores & transport oxygen. In hemoglobin, iron is present in ferrous form & complex with molecular oxygen.

I.Hemoprotein:

II.Iron storage protein:

Himosiderin & Ferritin are iron storag protein which are found in liver, spleen & bone marrow. In ferritin complexed iron is present as ferric (Fe+++) form, but it released in ferrous (Fe++) form. Himosiderin is dehydrated form of ferritin. Ferritin soluble in water where himosiderin is water insoluble.

III.Iron transport protein:

5

Transferrin is glycoprotein present in blood plasma act as iron transport protein. Two atoms of ferric ions bound to each molecule of glycoprotein. Regulation: Content of iron in body generally controlled by absorption & not by elimination. Daily requirement is quite low. Iron requirement increases during pregnancy, growth & lactation. Large ant. Of iron lost in hemorrhage & menstrual flow. Small amnt. Of iron excreted through urine & faces.

Sources:
a) Food b) Cow Milk c) Soybean substitute

DEFECIENCY DISEASES:
Anemia Iron preparations:
6

Number iron preparations are available in market like1. 2. 3. 4. Liquid orals Capsule Tablets Injectables

Iron poisoning: Overdose of iron can causes serious problem like iron poisoning. Four stages of iron poisoninga)Stage I- begins after 30-40 minutes after ingestion & includes GIT distress due to astringent action of ionized iron, developing into CVS collapse, shock & possible death in six hrs. b)Stage II- recovery seems apparent & may continue for 10-14 hrs.

c)Stage III- Develop with recurrent CVS collapse, convulsions, metabolic acidosis, shock, coma, liver damage & possible death. d)Stage IV- Occurs 1-2 months later with GIT complications due to necrotizing (cell death) effect of iron. TREATMENT OF IRON POISONING: Treated by gastric lavage, followed by giving sodium bicarbonate & sodium dihydrogen phosphate which convert iron into insoluble iron salt. Deferoxamine is orally administered to prevent absorption of iron. When Deferoxamine administered parenterally causes chelation of iron which passes through urine. Peritoneal dialysis

IRON COMPOUNDS8

I.FERROUS FUMERATE:
Mol. Formula: C4H2FeO4 Mol.Wt.- 169.9 Contains NLT 93% of C4H2FeO4

PREPARATION:

By double decomposition. A hot aqs. Soln. of ferrous sulphate is added to a soln. of sod. Fumerate with const. stirring. Sparingly soluble ferrous fumerate separate out.

PROPERTIES-

Reddish-orange or brown powder. Contains soft lumps which produces yellow stark when crushed.

Light odour Astringent taste Soluble in water & less in alcohol.

ASSAY:

Based on Oxidation-Reduction reaction. 0.3 gm sample is dissolved in 15 ml of dil. Sulphuric acid by gentle warming , cooled, add 50 ml water & immediately titrated with 0.1 M cerric ammonium sulphate using ferroin sulphate as indicator. Factor-Each ml of 0.1 M cerric ammonium sulphate=0.01699 gm of C4H2FeO4.

Uses: Anemia

II.FERROUS GLUCONATE:
10

Mol. Formula: C12H22O14Fe.2H2O Mol.Wt.- 428.7 Contains NLT 95% of C12H22O14Fe.2H2O as per IP & as per BP- NLT-11.80% & NMT-12.5%

PREPARATION:

By reacting ferrous carbonate with gluconic acid, which obtained by fermentation of glucose. C6H12O6 C6H12O7

PROPERTIES-

Yellowish grey or pale greenish-yellowish powder. Odour of burnt sugar. Soluble in water & insoluble alcohol. Aq. Soln. acidic in nature.

ASSAY:
11

Based on redox titration method. 1.5 gm of sub. is dissolved in mix. Of 75 ml water & 15 ml of 2 N sulphuric acid. About 0.75 gm of zinc powder is added, flask stoppered & set aside until soln. is decolourised. It is filtered, ppt. washed with 20 ml water & combine filtrate & washings titrated with 0.1 M cerric ammonium sulphate using ferroin sulphate as an indicator until colour changes from orange to green. Factor-Each ml of 0.1 M cerric ammonium sulphate=0.01699 gm of C12H22O14Fe.2H2O. Uses: Anemia

Mol. Formula: FeS04.7H20 Contains NLT 98% &

12

III. FERROUS SULPHATE:

PREPARATION:

Mol.Wt.- 278.0 NMT- 105% FeS04.7H20

By dissolving iron in dil. sulphuric acid. After the effervescence has stopped, the liquid is filtered, concentrated & cooled. The crystals formed are seperated. Fe + H2S04 + H20 FeS04.7H20 + 13H20

PROPERTIES-

Bluish green crystalline powder or transparent grren crystal. Odourless with metallic astringent taste. Expose to air it undergoes rapid oxidation. Soluble in water & insoluble alcohol. When heated it decomposes to ferric oxide, sulphur dioxide & sulphuric acid.
2(FeS04.7H20) Fe203+SO2+H2S04+13H2O

ASSAY:
13

Based on redox titration method. Previously , it was assayed by titrating with potassium permagnate in acidic medium. 2Fe3SO4 + 2KMnO4 + 4H2SO4K2SO4 + 2MnSO4+ Fe2 (SO4)3+4H2O Now it is titrated with cerric ammonium sulphate. Weigh accurately about 1 gm of sub. is dissolved in mix. Of 30 ml water & 20 ml of dil. sulphuric acid. And content titrated with 0.1 M cerric ammonium sulphate using ferroin sulphate as an indicator until colour changes from orange to green. Factor-Each ml of 0.1 M cerric ammonium sulphate=0.0278 gm of FeS04.7H20.

Uses:

Anemia

IV.IRON & DEXTRAN INJECTION (IP,BP):

14

Sterile colloidal soln. containing a complex of

ferric hydroxide with dextran of low mol. Wt. in

water for injection. It contains NLT 4.75% &

NMT 5.25% W/V of iron. It is sterilized by

heating in an autoclave. It is administered by

deep IM injection & usual dose in 1-2ml daily.

B.COPPER & ITS COMPOUNDS:

15

Another essential trace element required for normal metabolism in man & most animals. Generally requirement of copper provide food, water & cooking utensils, therefore copper supplements are not required. In adult- 2 mg/kg of copper estimated. It distributed in enzyme & proteins. Copper which is provided through food & water, it reaches to stomach, get solubilised & absorbed in stomach & upper portion of intestine. & excess is excreted. 4/5 is excreted through bile, about 1/6 through gut wall goes to intestine & small portion excreted through urine.

Copper moves to blood plasma from intestine, there it exist as copper-albumin complex. Copper then to liver where it exist as copper protein 16 goes ceruloplasmin.

Role of Copper:

I.To prevent anemic condition. II.In oxidative phosphorylation. III.Necessary for amine oxidase activity & play role in formation of elastine.

Deficiency diseases:

a) In children- Chronic diarrhea, Neutropenia. b) Wilsons disease- excessive storage causes liver cirrhosis, brain damage & kidney defects

OFFICIAL COPPER PRODUCTS:

Only Copper suphate is official in IP.
17

COPPER SUPHATE: Mol. Formula: CuS04.5H20 Mol.Wt.249.7 Contains NLT 98.5% & NMT- 101% CuS04.5H20

PREPARATION:

1).By treating copper in dil. sulphuric acid in presence of air. After the effervescence has stopped, the liquid is filtered, concentrated & cooled. The crystals formed are separated.
2Cu + 2H2S04 + 02 CuS04.5H20 + 2H20 2). By heating copper in furnace with sulphur. The mixture of copper sulphate & copper oxide obtained. Then it is treated with di. Sulphuric acid. The resulting soln. is filtered & concentrated & allow to crystallise.

PROPERTIESDeep Blue, triclinic crystals or blue crystalline granules or powder. 18 Odourless Nauseous & metallic taste. Effloresces slowly in dry air. Soluble in water & insoluble alcohol. Aq. Soln. is acidic to litmus paper.

Uses:

Emetic. Antidote for phosphorus poisoning. Ingredient of Benedict & Fehling reagent. Fungicidal. Astringent. Fungicidal & Algicidal in agriculture.

C.ZINC & ITS COMPOUNDS:

Widely distributed in body. Biochemically, it is 19 associated with certain metalloenzymes likeAlcohaol dehydrogenase Lactic dehydrogenase. Malate dehydrogenase D-lactate-cytochrome-C reductase Glyceraldehyde-3-phosphate dehydrogenase Glutamic dehydrogenase Aldolase Carbonic anhydrase Alkaline phosphtase Carboxy peptidase Neutral protease.

SOURSES:
20

Essential dietary mineral. requirement is 10-15 mg. Meat Milk Fish Nuts Legumes

Minimum

daily

DEFICIENCY:

Impaired growth Parakeratosis Retarded sexual maturation Alcoholic cirrhosis Active tuberculosis

Painless ulcers Uremia 21 Myocardial infarction Down syndrome Cystic fibrosis TOXICITY: Resulted from ingestion of acid food kept in galvanized metal container & workers inhaling zinc oxide. SymptomsChills Fever Malaise Coughing Salivation Headache

TreatmentChelation therapy with dimercaprol.

22

OFFICIAL ZINC PRODUCTS:

Two compounds are official in IP 1)Zinc Oxide 2)Zinc Sulphate

I.ZINC OXIDE:

Mol. Formula: ZnO Contains 99-100.5% of ZnO

Mol.Wt.- 81.38

PREPARATION:

1)Commercially-By heating metallic zinc in a current of air at high temp. The metal turns into oxide. 2Zn + O2 2ZnO

2)MedicinallyFrom Zinc sulphate by double decomposition. Zinc silphate is added to boiling soln. of sodium carbonate. 23 The ppted zinc carbonate is collected, washed until free from sulphate, dried & ignite. ZnSO4 + Na2CO3 ZnCO3 + Na2SO4 ZnCO3 ZnO + CO2

PROPERTIESWhite amorphous, fine powder. Odourless Tasteless. insoluble in water & alcohol but soluble in mineral acid & ammonia.

ASSAY:
24

Analysed by acidimetric back titration. ZnO is base, it insoluble in water & cannot titrated directly with acid. Therefore it is dissolved in excess of std. acid & excess acid is back titrated. Ammonium chloride is used in titration to prevent ppt. of zinc hydroxide. Methyl orange is used as indicator.

Uses:

Mild antiseptic. Astringent. Treatment of eczema, ringworm, varicose ulcer & psoriasis. In mfq. of adhesive tapes & bandages.

I.ZINC SULPHATE:
25

Mol. Formula: ZnSO47H20 Mol.Wt.- 287.54 Contains 99-108.0% of ZnSO47H20

PREPARATION:

1)Industry -By heating metallic zinc blend ( zinc sulphide) in the presence of air under specified condition. The heated mass is dissolved in hot water, filtered & the soln. concentrated for crystallisation. Zn + 2O2 ZnSO4 2)Commercially: By digesting metallic zinc granules in di. Sulphuric acid. The soln. is& treated with chlorine to oxidise any ferrous impurity into ferric sulphate which is then ppted. By hydroxide & removed. The filtrate is concentrate & crystallised. Zn + H2S04 ZnSO4 + H2

PROPERTIES26

Colourless transparent prism or small needles. May be Granular crystalline powder.

Odourless
Tasteless.

Effloresces slowly in dry air.

Soluble in water & glycerin, insoluble in alcohol.

Aq. Soln. is acidic to litmus paper.

When heated it decomposes.

Uses:
27

Emetic. Germicidal Styptic action. Protective Ophthalmic Astringent. Wound healing.

C.IODINE & ITS COMPOUNDS:

Iodine is one of essential trace element. Necessary for synthesis of two hormones produced by thyroid 28 gland- Triiodothyronine & Thyroxin. It can discussed from 2 standpoints1.Its biochemical role in thyroid hormone formation 2.Pharmacological action as fibrolytic, expectorant & bactericidal agent.

Necessary for synthesis of two hormones produced by thyroid gland- Triiodothyronine & Thyroxin. Thyroxin is storage form of hormone while Triiodothyronine is circulating form of iodine. Important function of thyroxin is to increase metabolic rate. Deficiency of this causes Hypothyroidism is condition in which metabolic processes are slowed down & Goiter, Cretinism ( dwarfism).

29

Hyperthyroidism is condition in which excessive secretion of thyroid hormones & severe form of this is minifested by Exopthalamus. It is treated by antithyroid drugs like carbimazole & methimazole. While Hypothyroidism is treated by suitable iodine compounds like sodium iodide or potassium iodide. RequirementMan-Average is about 140 micrograms. Female- about 100 micrograms daily. Administration- administered internally which is reduced to iodide. After administration of iodine its uptake is governed by various factor likea)Condition of local thyroid tissue. b)Concentration of inorganic iodide in blood c)An anterior pituitary hormone thyrotropin level in blood.

DEFICIENCY:
Endemic goiter.
30

OFFICIAL IODINE PRODUCTS:

1. IODINE: Mol. Formula: I2 Mol.Wt.- 253.8 Contains 99.5-100.5% W/W of I2

PREPARATION:

By extracting kelp (seaweed ash) with water & the soln. is concentrated. The sulphate & chloride of sodium, potassium are crystallized out, leaving freely soluble sodium & potassium iodide in mother liquor. Sulphuric acid is added to mother liquor & sulphur which is liberated from small amnt. of thiosulphate & sulphide is allowed to settle. The mother liquor is decanted & to this Mno2 is added & iodine is distilled out. 2NaI + 3H2SO4 + MnO2 MnSO4 + 2NaHSO4+ I2+ 2H20

PROPERTIESHeavy, bluish black rhombic prism or plates with 31 metallic luster. Peculiar odour. Volatalises at ordinary temperature. At high temp. it melts. Insoluble in water but soluble in alcohol. Freely soluble in chloroform & solvent ether. Chemical properties areCombines directly with some non-metals & many metals. 2P + 3I2 2PI3 Fe + I2 FeI2

Reducing agents react with aq. Iodine soln. & get oxidised. 32 H3ASO3 + I2 + H2O 2HI + H3ASO4 H2S + I2 2HI + S Reacts with alkali to form an iodide & iodate when heated. I2 + 6NaOH 5NaI + NaIO3 + 3H20 KI dissolve large qty. of iodine because formation of I3- ion. KI + I2 KI3

Analysed by oxidation-reduction titration. About 0.5 gm of iodine is dissolved in a soln. of pot. Iodide in 5 33 ml of water in iodine flask, diluted with 50 ml water acidified with 1 ml of acetic acid & Titrated with 0.1 N sodium thiosulphate soln. using starch as indicator. Factor- Each ml of 0.1 N sodium thiosulphate = 0.01269 gm of iodine.

ASSAY:

Uses:

Aq. & alcoholic soln. used as germicidal & fungicidal. Treatment of Throtoxicosis. Purification of drinking water. Bactericidal & amoebicidal. Antidote in alkaloid poisoning. In TLC used as locating agent In oxidation reduction titrations. Storage- well closed amber coloured bottle.

2.SODIUM IODIDE:
34

Mol. Formula: I2 Mol.Wt.- 253.8 Contains 99.5-100.5% W/W of I2

PREPARATION:

By adding slight excess iodine to the concentrated soln. of sod. Hydroxide. This gives a mix. of sodium iodide & sod. Iodate. Reaction mix. Is evaporated to dryness & residue is treated with carbon to convert sodium iodate to sod. iodide. 6NaOH + 3I2 5NaI + NaIO3 + 3H2O NaIO3 + 3C NaI + 3CO

PROPERTIES-

White crystalline powder or colourless crystal. Odouress. Hydroscopic in nature. soluble in water & alcohol.

ASSAY:
Sodium iodide soln. is titrated with pot. Iodate 35 soln. in acidified media, iodine is liberated. Under high concentration of HCl the liberated iodine is converted into iodine monochloride. The endpoint is indicated by disappearance of iodine colour from chloroform layer. Method- About 1.3 gm of sod. Iodide is dissolved in 100ml water. 20 ml of this soln. is taken in iodine flask, 40 ml conc. HCl is added & contents titrated with 0.5 m pot. Iodate until colour changes to yellow. 5 ml chloroform is added & titration continued with shaking against pot. Iodate until chloroform layer is colourless. Factor- Each ml of 0.05 M Pot. Iodate = 0.01499gm of NaI

Uses:
36

Remedy for thyroid gland disorder. Fibrolytic agent in syphilis & leprosy. Antifungal & actinomycosis. Anti TB. Expectorant Asthma & chronic bronchitis.

There are several radioactive isotopes of iodine & 37 out of that 131 I is most used. 131I is obtained by neutron irradiation of tellarium & used in form of sod. Iodide. 131 I is official in BP. It is aq. Soln. containing iodine 131 I in the form of sod. Iodide & contains sod. Thiosulphate or any other reducing agent. The content of 131I is NLT-90% & NMT- 110. The sp. Activities are NLT-185 GB per mg of iodine. PREPARATION: 131I is obtained by neutron irradiation of tellarium & used in form of sod. Iodide. PROPERTIESColourless soln. Half life-8.04 days. Emits beta & gamma radiation. pH in between 7-10.

3.RADIOACTIVE IODINE & SODIUM IODIDE:

ASSAY:
The activity is determined by comparison with std. 38 iodine 131 soln. Sodium iodide soln. is titrated with pot. Iodate using any suitable counting instrument. It is also tested for radio nuclide purity & radiochemical purity.

USES:

Diagnosis of thyroid function disorder. Treatment of hyperthyroidism & goiter. Graves disease. Metastate thyroid cancer.