Aspirin salicylic acid and

Determination of various analgesic and antipyretic pharmaceuticals on reversed phase has included not only the analysis of serum levels of aspirin, salicylic acid and salicyluric acid using acidified acetonitrile (557), or methanol (338), but also suUinpyrazone under isocratic conditions (339), and 6-chloro-a-methylcarbazole-2-acetic acid (340). The polar thiol metabolites of acetaminophen were analyzed by RPC and the method was found to be superior to other chromatographic techniques used in this analysis (341). 

Quantification. Gas Chromatography. In plasma aspirin, salicylic acid, and salicylamide, detection limit 200 to 500 ng/ml for all three compounds, FID—M. J. Ranee et al., J. Pharm. Pharmac., 1975,27,425-429. 

High Pressure Liquid Chromatography. In plasma aspirin, salicylic acid, and salicyluric acid, sensitivity 50ng/ml for aspirin in plasma also aspirin metabolites in urine, UV detection—J. N. Buskin eta/., Clin. Chem., 1982,28,1200-1203. In plasma or urine aspirin and its major metabolites, detection limits in plasma lOOng/ml for aspirin and salicyluric acid, 500 ng/ml for salicylic acid, and 200 ng/ml for gentisic acid, UV detection—R. H. Rumble et a/., J. Chromat., 1981,225 Biomed. AppL, 14, 252-260. 

In another study, the kinetics of aspirin, salicylic acid, and salicyluric acid were followed upon oral... 

Mason WD, Winer N. Kinetics of aspirin, salicylic acid and salicyluric acid following oral administration of aspirin as a tablet and two buffered solutions. ] Pharm Set 1981 70(3) 262-265. 

A) Acetylsalicylic Add (Aspirin). Salicylic acid and its derivatives were among the first synthetic organic compounds to be used for therapeutic purposes. The sodium salt of salicylic acid, the methyl and phenyl esters, and the acetyl derivative of salicylic acid are extensively used to diminish pain (as analgesics) and to reduce the temperature of the body (as antipyretics). The most widely used is the acetyl derivative which is sold under the name aspirin. Salicylic acid is prepared industrially by the carbonation of sodium phenoxide, at 180-200° at atmospheric pressure or 120-130° at a pressure of a few atmospheres. 

Paterson has proposed that natural salicylates contribute to the recognized benefits of a healthy frait and vegetable diet. Salicylic acid is responsible for the anti-inflammatory action of aspirin, and it may cause the reduced risk of colorectal cancer observed in those who take aspirin. Salicylic acid and other salicylates occur naturally in fruits and plants, and diets rich in these are beheved to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than nonvegetarians, and there is overlap between concentrations in vegetarians and those taking low-dose aspirin However, Janssen et al. concluded that the content of (acetyl)salicyhc acid in diets may be too low to affect disease risk. Additional work is needed to confirm this concept. 

The key compound m the synthesis of aspirin salicylic acid is prepared from phe nol by a process discovered m the nineteenth century by the German chemist Hermann Kolbe In the Kolbe synthesis also known as the Kolbe—Schmitt reaction, sodium phen oxide IS heated with carbon dioxide under pressure and the reaction mixture is subse quently acidified to yield salicylic acid... 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

The salicylates include aspirin (acetylsalicylic acid) and related drugp, such as magnesium salicylate and sodium salicylate. The salicylates have analgesic (relieves pain), antipyretic (reduces elevated body temperature), and anti-inflammatory effects. All the salicylates are similar in pharmacologic activity however, aspirin has a greater anti-inflammatory effect than the other salicylates. Specific salicylates are listed in the Summary Drug Table Nonnarcotic Analgesics Salicylates and Nonsalicylates. 

Suppose a chemist started with 152 g of salicylic acid and 86.8 g of acetic anhydride and produced 133 g of aspirin. What is the yield of this reaction ... 

Erdmann and Uhrich (2000 Erdmann et al., 2000) recently synthesized novel poly(anhydride-co-ester)s containing salicylic acid in the backbone, by melt polycondensation of the disalicylic acid ester of sebacic acid, poly[bis(o-carboxyphenoxy)sebacate] (PCPS) and the copolymer P(CPH-CPS). The release of salicylic acid (the active form of aspirin) from the former was studied in vitro and from the latter was studied in vivo (Erdmann and Uhrich, 2000 Erdmann et al., 2000). Similar polymers that release 5-amino salicylic acid, and p-nitro salicylic acid have been prepared... 

It is easily forgotten that aspirin degrades to acetic as well as salicylic acid. And, indeed, any smell aspirin might have is due to acetic acid. However, the volatility of acetic acid does not make the determination of acetic acid a reliable tool to measure stability or degradation. 

In 1911, Neuberg186 detected small amounts of gentisic acid (2,5-dihydroxybenzoic acid) in the urine of dogs dosed with aspirin. The metabolism of aspirin is intertwined with that of salicylic acid, but I was unable to ascertain who first reported the metabolic formation of salicyluric acid, the major metabolite of both salicylic acid and aspirin, specifically after administration of aspirin. 

Aspirin Salicylic Acid Dissolve 2.5 g in 25 ml alcohol (TS). To each of two matched cylinders add 48 ml of water and 1 ml of freshly prepared Ferric Ammonium Sulph. Reagent1. Into one cylinder pippete 1 ml of stand, salicylic acid soln. (0.01 % w/v in water) and into the other pipette 1 ml of TS. Mix the contents of the cylinder, after 30 secs, the colour of the second cylinder is not more intense than the first cylinder. NMT 0.1... 

The second method is when TLC is used to compare an unknown substance with the pure substance. For example, an aspirin sample prepared in the laboratory could be compared with a pure sample of aspirin. Three spots are made on the baseline of the TLC plate one of the laboratory-prepared aspirin, a second of a sample of pure acetyl salicylic acid, and a third of a sample of both the laboratory and the pure samples (a co-spot). Once the plate has been developed, analysis is carried out by comparison. If the co-spot shows only one spot, it can be concluded that the laboratory-synthesised sample is exactly the same compound as the pure substance. 

Various processes involve acetic acid or hydrocarbons as solvents for either acetylation or washing. Normal operation involves the recovery or recycle of acetic acid, any solvent, and the mother liquor. Other methods of preparing aspirin, which are not of commercial significance, involve acetyl chloride and salicylic acid, salicylic acid and acetic anhydride with sulfuric acid as the catalyst, reaction of salicylic acid and ketene, and the reaction of sodium salicylate with acetyl chloride or acetic anhydride. 

Aspirin (acetylsalicylic acid) and other salicylates are still a common cause of human poisoning, both therapeutic and suicidal, and account for a significant number of deaths each year. Although the toxic effects have a biochemical basis, some of the effects caused are clearly physiological, and consequently, it has been used as an example in this category. 

The active principle was shown to be salicin by Buchner in 1828 but the bitter taste and damage to the gastric mucosa limited its use. Piria isolated salicylic acid from salicin in 1838. In 1859, Kolbe discovered the structure and synthesis of salicylic acid and in 1897 acetylsalicylic acid was synthesized by Hoffmann. Two years later, in 1899, acetylsalecylic acid, the first nonsteroidal antiinflammatory drug was registered under the name Aspirin (Fig. 2). 

See also Aspirin and Salicylic Acid and Related Compounds. 

It was found that salicylic acid in its pure form had a number of defidencies, and for a number of years chemists sought a salicylic acid-based compound that would be effective yet less harsh and that could counteract pain with smaller dosages. This process ended in 1898 with the introduction by Bayer of acetylsalicylic acid, which has the formula C6H4(COOH)C02CHs and since then has been commonly referred to as aspirin, See also Acetylsalicylic Acid and Salicylic Acid and Related Compounds. 

Flow ever, this method is applied only when esterification eannut be effected by the usual acid-alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate. See also Fibers Cellnlose Esters, phenyl acetate (used in aceLaminophen production), and aspirin (acctylsalicylic acidl (see also Salicylic Acid and Related Compounds are examples of the large-scale use of acetic anhydride. 

Bose et alm have demonstrated the synthesis of aspirin from salicylic acid and acetic anhydride using commercial microwave reactors (Scheme 9.6). Without optimising the conditions, high purity aspirin was obtained in greater than 80% yield (500-800 g scale). 

The relationship between gastric residence time (GRT) and the variability in aspirin absorption from enteric-coated tablets has also been evaluated with the Heidelberg capsule [59], The study design was a single dose crossover study with men and women, fasted and fed. In addition to pH monitoring, plasma concentrations of salicylic acid and salicyluric acid in plasma and urine were measured. GRT was significantly delayed in the fed state, and women had longer GRT compared with men. 

In this process, a 500-gallon glass-lined reactor is needed to heat the salicylic acid and acetic anhydride for 2 to 3 hours. The mixture is transferred to a crystallizing kettle and cooled to 3°C. Centrifuging and drying of the crystals yields the bulk aspirin. The excess solution is stored and the acetic acid is recovered to make more acetic anhydride. 

FIGURE 1 Chemistry of salicylic acid and aspirin production. 

---