Free salicylate

I. Methyl salicylate test. Heat i ml. of methanol with 0 5 g. of sodium sdicylate (or free salicylic acid) and a few drops of cone. H2SO4 gently for i minute. Cool, pour into a few ml. of cold water in a boiling-tube, and shake. Note the odour of methyl salicylate (oil of wintergreen). 

On the other hand, since the angular derivative 19, whose constitution is characterized by two quasi-isolated hydroxynaphthalenecarboxylic acid subunits and whose structural analogy to a pair of scissors is removed for the most part, also yields an inclusion compound with dimethylformamide with strict stoichiometry of 1 237), and only and exclusively this one (Table 3), it is obvious that the free salicylic acid unit might be the decisive factor for the preferred binding of dimethylformamide of this class of compounds. 

In contrast to aspirin itself, the U.S.P. monograph for aspirin tablets has undergone considerable changes. For some reason, U.S.P. does not use the ferric salt test for free salicylic acid, as does the British Pharmacopeia of 1973. Apparently, certain excipients such as citric and tartaric acid interfere with this reaction.77 Already in 1913, a double titration method was developed78 which was made an official method in 1926.79 This method was used as the assay method when the aspirin tablets monograph was introduced into U.S.P. XII in 1942. 

As has already been pointed out, the determination of salicylic acid is intricately interwoven with that of aspirin itself. There is the convenient color reaction with ferric chloride which was already used by Dreser1 to determine free salicylic acid in his own urine after the ingestion of aspirin. However, this reaction is not too specific and considerable work has gone in the development of interference free methods. 

MAGNESiUM SALiCYLATE A sodium free salicylate derivative that may have a low incidence of Gl upset. The product labeling and dosage are expressed as magnesium salicylate anhydrous. The possibility of magnesium toxicity exists in people with renal insufficiency. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

Acetylsalicylic acid Vitamin C Free acetic acid Free salicylic acid... 

The content of free salicylic acid remained always below 0.2 %. 

That the discovery of the patentee was a most valuable one clearly appears. Even a small amount of free salicylic acid injures the stomach but, if this can be taken out, the acid is not dissolved in the stomach and does not injure it, but is held in bond intact until it reaches the lower digestive tract. While the discoveries of Von Gilm, Kraut, and others were known for many years before 1898, yet no extensive practical use was ever made of them, while the patented product went into immediate use and so continues on a large scale. 

Iron(III) chloride solution intense violet-red colouration with neutral solutions of salicylates or with free salicylic acid the colour disappears upon the addition of dilute mineral acids, but not of a little acetic acid. The presence of a large excess of many organic acids (acetic, tartaric, and citric) prevents the development of the colour but the addition of a few drops of dilute ammonia solution will cause it to appear. 

Indications. A red colour indicates the presence of free salicylic acid. 

Figure 4.16 shows the increased generation of free salicylic acid at 37°C in the tablets containing paracetamol, it is interesting to note from this figure the effect on stability of tablet excipients. Addition of 1% talc caused only a minimal increase in the decomposition,... 

Figure 4.16 Development of free salicylic acid in aspirin-paracetamol-codeine and aspirin-phenacetin-codeine tablets at37X.

In solution, particularly in the presence of stxiium bicarbonate. the salt will darken on standing (see salicylic acid). This darkening may be lessened by the addition of sodium sulfite or sodium bisulfite. Also, use of recently boiled distilled water and dispensing in amber-colored bottles lessens color change. Sodium salicylate forms a eutectic mixture with antipyrine and produces a violet coloration with iron or its salts. Solutions of the compound must be neutral or slightly basic to prevent precipitation of free salicylic acid. The USP salt forms neutral or acid solutions, however. 

This. salt is the one of choice fur salicylate medication and usually is administered with stxiium bicarbonate to le.ssen gastric distress, or it is administered in enteric-coated tablets. The u.se of sodium bicarbonate is ill advised because it decreases the plasma levels of salicylate and increases the excretion of free salicylate in the urine. 

Magnesium Salicylate, USP. Magnesium. salicylate (Mobidin. Magan) is a. stHlium-free salicylate preparation for use when sodium intake is restricted. It is claimed to produce le.ss gastrointestinal upset. The dosage and indications are the same us those for sodium. salicylate. 

Heideman et. ah (51) developed a rapid HPLC method for the estimation of salicylic acid in aspirin tablets. Method involves the blending of tablets with acidic ethanol to extract the aspirin and salicylic acid rapidly. The resulting preparation is then immediately injected on to a 4.6 mm x 3 cm 5 micron reverse-phase column. Aspirin and free salicylic acid are determined simultaneously. The run time is less than 2 minutes. 

With the objective of preparing water-soluble salts of aspirin (which is known to be badly soluble in water and anyway rapidly hydrolyzed), the chemists of TEquilibre Biologique prepared and patented some aspirin salts of the basic amino-acids lysine and arginine which were provided by AEC (French patent 1 295 304, May 7th, 1956). The salts proved to be water-soluble, but the laboratory procedure used for their preparation yielded slightly hygroscopic salts which partly decomposed to acetic acid and free salicylic acid. The industrial development was therefore precluded for some years. 

Powder with greater hulk density and relatively Low free salicylic acid content as compared with other aluminum salicylates. Rates of soln of aspirin from aloxiprin in buffer sol ns of pH 2-8 are lower than those of aspirin, particularly in more acid buffers. 

Extremely hygroscopic solid, mp 49.5-50,0°. Very freely tel in water. Also sal jn alcohol, acetone, other hydrophilic solvents. Practically insol in ether, petr ether, benzene, oils. Aq solns are stable, they contain the eompd in the form of its dissociated choline and salicylate ions. pH of 10% aq soln 6.5. Aq solns are easily discolored by minute traces of iron. The addition of acid to aq solns immediately precipitates free salicylic add, while choline base, readily recognized by its fishy odor, is libsrated upon the addition of alkali. 

Roughly 80-90% of the salicylate in plasma is bound to proteins, especially albumin, at concentrations encountered clinically the proportion of the total that is bound declines as plasma concentrations increase. Hypoalbuminemia, as may occur in rheumatoid arthritis, is associated with a proportionately higher level of free salicylate in the plasma. Salicylate competes with a variety of compounds for plasma protein binding sites these include thyroxine, triiodothyronine, penicillin, phenytoin, sulfinpyrazone, bilirubin, uric acid, and other NSAIDs such as naproxen. 

It is considered to be one of the choicest drug specifically for salicylate medieation and is usually administered with either sodium bicarbonate to minimise effeetively the gastric distress or as enteric-coated dosage forms. However, the usage of NaHCOj is not advisable as it is found to retard the plasma levels of salicylate and enhances the elimination of free salicylate in the urine. 

Unfortunately, at this point, interpreting results for the electrode measurement of salicylate in blood samples is complicated by the fact that a large fraction of the total salicylate is bound to proteins (22, 23). The Sn(TPP)Cl2 based membrane electrode detects "free" salicylate while the conventional colorimetric procedure (i.e. the Trinder method (21) or variations thereof) measures total salicylate concentration (free plus bound). The former is the physiologically active form of the compound (24). Thus, the salicylate selective electrode could provide a new analytical tool for scientists who are examining the pharmacological effects of aspirin and other... 

It has been possible with the help of TLC, to detect diplosal (salicyl-salicylic acid) in free salicylic acid [9]. The impurities, chloroacetanilide and acetanilide, could similarly be detected in phenacetin [57 a, 143, 164a]. 

---