Acknowledgement

I wish to express my deep gratitude and sincere thanks to our Principal, Mrs. GEETHA BALACHANDER, D. A. V. Boys Senior Secondary School, Gopalapuram, Chennai 600 086 for her encouragement and for all the facilities that she provided for this project work. I sincerely appreciate this magnanimity by taking me into her fold for which I shall remain indebted to her. I extend my hearty thanks to my Chemistry Teacher Mrs. A. Charulatha, who guided me to the successful completion of this project. I take this opportunity to express my deep sense of gratitude for her valuable guidance, constant encouragement, constructive comments, sympathetic attitude and immense motivation, which has sustained my efforts at all stages of this project work.

I cant forget to offer my sincere thanks to the supporting staff Mr. S.K. Ravi, to my classmates and my brother J. ARVINTHRAM who helped me to carry out this project work successfully & for their valuable advice & support, which I received from them time to time. J. ABHINAVARAM

DEDICATION I DEDICATE THIS PROJECT WORK TO THE LOTUS FEET OF MY FATHER Mr. A. JAYARAMAN & MY MOTHER Mrs. A.A. MANGAYARKARASI.

Bonafide Certificate

Register No. Internal Assessment ___ 20

Certified to be the Bonafide Project work in Chemistry done by J. ABHINAVARAM of Class XII Section C of D. A. V. Boys Senior Secondary School, Gopalapuram, Chennai 600 086 during the year 2011 2012. Signature of Principal______________________ Teacher:__________________ School Seal Signature of subject

Submitted for the Practical Examination held on __ February, 2012 at D. A. V. Boys Senior Secondary School, Gopalapuram, Chennai 600 086.

Internal Examiner External Examiner

Chief Superintendent

Date:

WHY I CHOSE THIS PROJECT

This project introduces some knowledge about the basics involved in finding the constituents of PARACETAMOL. This Project deals with the principle of THIN LAYER CHROMATOGRAPHY.

Significance of project: Deals with analysis of PARACETAMOL Provides all basic ideas about THIN LAYER CHROMATOGRAPHY Provides information about ion exchange reaction

This project indeed would be a revolution in the world where there is increasing problem of adulteration of paracetamol tablets which are used all over the globe as analgesics by people of all age groups.

Introduction
Paracetamol or acetaminophen is a widely used over-the-

counter analgesic (pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with Opioid analgesics, paracetamol can also be used in the management of more severe pain such as post-surgical pain and providing palliative care in advanced cancer patients.[ The onset of analgesia is approximately 11 minutes after oral administration of paracetamol, and its half-life is 14 hours. While generally safe for use at recommended doses (1,000 mg per single dose and up to 3,000 mg per day for adults), acute overdoses of paracetamol can cause potentially fatal liver damage and, in rare

individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand. It is the active metabolite of phenacetin, once popular as an analgesic and antipyretic in its own right, but unlike phenacetin and its combinations, States, paracetamol Japan, is not Korea, considered carcinogenic at Hong Kong, and Iran) therapeutic doses. The words acetaminophen (used in the United Canada, South and paracetamol (used elsewhere) both come from a chemical name for the compound: para-acetylaminophenol. In some contexts, it is simply abbreviated as APAP, for acetyl-Para-aminophenol.

Theory Mechanism of Action

Metabolite of paracetamol

Anandamide Endogenous cannabinoid To date, the mechanism of action of paracetamol is not completely understood. The main mechanism proposed is the inhibition of cyclooxygenase (COX), and recent findings suggest that it is highly selective for COX-2. While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs, its peripheral antiinflammatory activity is usually limited by several factors, one of which is high level of peroxides present in inflammatory lesions. However, in some circumstances, even peripheral anti-inflammatory activity comparable to other NSAIDs can be observed. An article[ in Nature Communications from a research group in Lund, Sweden in November 2011 has found a hint to the analgesic mechanism of acetaminophen (paracetamol), being that the metabolites of acetaminophen e.g. NAPQI, act on TRPA1-receptors in the spinal cord to suppress the signal transduction from the superficial layers of the dorsal horn, to alleviate pain. Because of its selectivity for COX-2 it does not significantly inhibit the production of the pro-clotting thromboxanes. The COX family of enzymes is responsible for the metabolism of arachidonic acid to prostaglandin H2, an unstable molecule that is, in turn, converted to numerous other pro-inflammatory compounds.

Classical anti-inflammatories such as the NSAIDs block this step. Only when appropriately oxidized is the COX enzyme highly active. Paracetamol reduces the oxidized form of the COX enzyme, preventing it from forming pro-inflammatory chemicals. This leads to a reduced amount of Prostaglandin E2 in the CNS, thus lowering the hypothalamic set-point in the thermoregulatory centre. Paracetamol also modulates the endogenous cannabinoid system. Paracetamol is metabolized to AM404, a compound with several actions; what is most important is that it inhibits the uptake of the endogenous cannabinoid/vanilloid anandamide by neurons. Anandamide uptake would result in the activation of the main pain receptor (nociceptor) of the body, the TRPV1 (older name: vanilloid receptor). Furthermore, AM404 inhibits sodium channels, as do the anesthetics lidocaine and procaine. Either of these actions by themselves has been shown to reduce pain, and are a possible mechanism for paracetamol. However, it has been demonstrated that, after blocking cannabinoid receptors with synthetic antagonists, paracetamols analgesic effects are prevented, suggesting its painrelieving action involves the endogenous cannabinoid system. Spinal TRPA1 receptors have also been demonstrated to mediate antinociceptive effects of paracetamol and 9tetrahydrocannabiorcol in mice. The exact mechanisms by which COX is inhibited in various circumstances is still a subject of discussion. Because of differences in the activity of paracetamol, aspirin, and other NSAIDs, it has been postulated that further COX variants may exist. A recently discovered COX-1 splice variant termed COX-3 was considered to explain some of the knowledge gap but newer findings do not support the hypothesis that it plays any significant role in the functioning of paracetamol. Aspirin is known to inhibit the cyclooxygenase (COX) family of enzymes and, because paracetamols action is partially similar to aspirins, much research has focused on whether paracetamol also inhibits COX. It is now clear that paracetamol acts via at least two pathways. One theory holds that paracetamol works by inhibiting the COX3 isoform of the COX family of enzymes. When expressed in dogs, this enzyme shares a strong similarity to the other COX enzymes, produces pro-inflammatory chemicals, and is selectively inhibited by paracetamol.[68] However, some research has suggested that, in humans and mice, the COX-3 enzyme is without inflammatory action. Another possibility is that paracetamol blocks cyclooxygenase (as in aspirin), but that is in an inflammatory environment where the concentration of peroxides is high, and the high oxidation state of paracetamol prevents its actions. This would mean that paracetamol has no direct effect at the site of inflammation, but instead acts in the

CNS where the environment is not oxidative, to reduce temperature, etc. The exact mechanism by which paracetamol is believed to affect COX-3 is disputed.

Structure and reactivity

Paracetamol

molecule polar surface area Paracetamol consists of a benzene ring core, substituted by one hydroxyl group and the nitrogen atom of an amide group in the Para (1,4) pattern. The amide group is acetamide (ethanamide). It is an extensively conjugated system, as the lone pair on the hydroxyl oxygen, the benzene pi cloud, the nitrogen lone pair, the p orbital on the carbonyl carbon, and the lone pair on the carbonyl oxygen are all

conjugated. The presences of two activating groups also make the benzene ring highly reactive toward electrophilic aromatic substitution. As the substituents are Ortho, Para-directing and Para with respect to each other, all positions on the ring are more or less equally activated. The conjugation also greatly reduces the basicity of the oxygen and the nitrogen, while making the hydroxyl acidic through delocalization of charge developed on the phenoxide anion.

Synthesis In the laboratory, paracetamol is easily prepared by nitrating phenol with sodium nitrate, separating the desired p-nitro phenol from the ortho- byproduct, and reducing the nitro group with sodium borohydride. The resultant p-aminophenol is then acetylated with acetic anhydride. In this reaction, phenol is strongly activating, thus the reaction requires only mild conditions (cf. the nitration of benzene). The industrial process is analogous, but hydrogenation is used instead of the sodium borohydride reduction.

A simpler synthesis by Hoechst-Celanese involves direct acylation of phenol with acetic anhydride catalyzed by HF, conversion of the ketone to a ketoxime with hydroxylamine, followed by the acidcatalyzed Beckmann rearrangement to give the amide.

Demand for paracetamol in the United States was estimated at 3035 thousand tonnes per year in 1997, equal to the demand from the rest of the world.[74]

Uses
Medicinal Uses Fever Paracetamol is approved for reducing fever in people of all ages. The World Health Organization (WHO) recommends that paracetamol only be used to treat fever in children if their temperature is greater than 38.5 C (101.3 F). The efficacy of paracetamol by itself in children with fevers has been questioned and a meta-analysis showed that it is less effective than ibuprofen. Paracetamol has a well-established role in pediatric medicine as an effective analgesic and antipyretic.

Pain Paracetamol is used for the relief of pains associated with many parts of the body. It has analgesic properties comparable to those of aspirin, while its antiinflammatory effects are weaker. It is better tolerated than aspirin in patients in whom excessive gastric acid secretion or prolongation of bleeding time may be a concern. Available without a prescription, it has in recent years increasingly become a common household drug. Paracetamol can relieve pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. It is as effective as the non-steroidal anti-inflammatory drug ibuprofen in relieving the pain of osteoarthritis of the knee. Paracetamol has relatively little anti-inflammatory activity, unlike other common analgesics such as the NSAIDs aspirin and ibuprofen. Regarding comparative efficacy, studies show conflicting results when

compared to NSAIDs. A randomized controlled trial of chronic pain from osteoarthritis in adults found similar benefit from paracetamol and ibuprofen. The efficacy of paracetamol when used in a combination form with weak opioid (such as codeine) has been questioned by recent data studies; the small amount of data available has made reaching a conclusion difficult. Combination drugs of paracetamol and strong opioid like morphine have been shown to reduce the amount of opioid used and improve analgesic effect as well as discouraging overuse of addictive opioid due to APAPs potentially toxic effects. A randomized controlled trial of acute musculoskeletal pain in children found that the standard over-the-counter dose of ibuprofen gives greater pain relief than the standard dose of paracetamol.

Side Effects of Paracetamol Tablet

High dose-usage (greater than 2,000 mg per day) of paracetamol increases the risk of upper gastrointestinal complications like stomach bleeding.

Heavy use of paracetamol (300 grams a year or 1 g per day on average) can lead to a condition known as Small Indented and Calcified Kidneys (SICK).

Administering paracetamol for fever in the first year of life can lead to an increase in the incidence of asthmatic symptoms and an increased incidence of rhino conjunctivitis and eczema at 67 years.

Paracetamol used excessively damages multiple organs, particularly the liver and kidney where toxicity from paracetamol is not from the drug itself but from one of its metabolites.

Paracetamol toxicity is the most common cause of acute liver failure. This is one of the most dangerous side effects of

paracetamol. Habitual use of paracetamol leads to decrease in threshold for pain in a person. This means that the endurance level for pain reduces in that person.