Dermatological Agent, Analgesic
Synonyms. Acido Ortóxibenzoico; Acidum Salicylicum; Salizylsäure.
Proprietary names. It is an ingredient of many proprietary preparations—see Martindale, The complete drug reference, 33rd Edn, London, Pharmaceutical Press, 2002.
Colourless, feathery crystals or a white crystalline powder. M.p. 159°.
Soluble 1 in about 550 of water, 1 in about 4 of ethanol, 1 in 45 of chloroform, and 1 in 3 of ether.
Synonym. (2-Hydroxyethyl)trimethylammonium Salicylate
Proprietary names. Arthropan; Audax; Teejel. It is an ingredient of Bonjela.
A white, crystalline, very hygroscopic powder. M.p. 49.5° to 50.0°.
Very freely soluble in water; soluble in ethanol and acetone; practically insoluble in ether, petroleum ether, benzene, and oils.
Synonym. Sodium 2-Hydroxybenzoate
Proprietary names. Dodds; Jackson’s Febrifuge. It is an ingredient of Cystex, Doans Backache Pills, and TCP Cream.
Colourless crystals, crystalline flakes, or white or faintly pink powder. M.p. 440°.
Soluble 1 in 1 of water and 1 in 11 of ethanol; practically insoluble in chloroform and ether. Concentrated aqueous solutions are liable to deposit crystals of the hexahydrate on standing.
pKa3.0, 13.4 (25°).
Log P(octanol/water), 2.3.
Ferric Chloride—blue–violet; Folin–Ciocalteu Reagent—blue; McNally’s Test—red.
System TD—Salicylic acid Rf 07, salicyluric acid Rf 00; system TE—salicylic acid Rf 10, salicyluric acid Rf 00; system TF—salicylic acid Rf 01, salicyluric acid Rf 00; system TAD—Rf 24; system TAE—Rf 86; system TAJ—Rf 12; system TAK—Rf 71; system TAL—Rf 70. (Location under UV light, violet fluorescence; ferric chloride solution, violet; acidified potassium permanganate solution, positive.)
System GA—Salicylic acid RI 1307, salicylic acid-Me RI 1200, salicylic acid-Me2 RI 1195, M (glycine conjugate) RI 1825, M (glycine conjugate)-Me RI 1810, M (glycine conjugate)-Me2 RI 1845; system GB—salicylic acid RI 1340, salicylic acid-Me RI 1228; system GL—salicylic acid-Me2 RI 1210, M (5-OH-)-Me3 RI 1530.
High Performance Liquid Chromatography.
System HD—salicylic acid k 0.7, choline salicylate k 0.7; system HW—salicylic acid k 4.6, choline salicylate k 4.8; system HX—RI 350; system HY—RI 355; system HAA—Retention time 12.1 min; system HAX—Retention time 5.2 min; system HAY—Retention time 4.4 min.
Aqueous acid—236 (A11=647a), 303; aqueous alkali—298 (A11=259a). Choline salicylate: methanol—298 nm (A11=170b). (See below)
Principal peaks at wavenumbers 758, 1657, 1288, 1210, 1250, 1150 (salicylic acid, KBr disk); 1587, 1724, 1176, 1515, 699, 1041 cm−1 (choline salicylate).
Principal ions at m/z 120, 92, 138, 64, 39, 63, 121, 65; salicyluric acid 121, 120, 69, 92, 195, 39, 93, 45.
Salicylic Acid: Clarke’s Analysis of Drugs and Poisons
Disposition in the Body.
Rapidly absorbed and distributed throughout the body. Metabolised by conjugation with glucuronic acid and glycine to give salicyluric acid, salicyl O-glucuronide, and salicyl ester glucuronide; hydroxylation to gentisic acid, gentisuric acid, and dihydroxy and trihydroxy derivatives also occurs. Excreted in the urine as unchanged drug and metabolites.
Salicylic acid is the major metabolite of aspirin, methyl salicylate, and salsalate.
Following daily oral doses of 9 mg/kg of sodium salicylate to 20 female and 20 male subjects, mean peak plasma concentrations of 57 and 58 mg/L were attained in 0.9 and 0.5 h respectively [S. L. Miaskiewicz et al.,Clin. Pharmacol. Ther.,1982, 31, 30–37].
After daily oral doses of choline salicylate, equivalent to 3.8 g of aspirin, a mean steady–state serum concentration of 166 mg/L was reported [P. D. Hansten and W. L. Hayton,J. Clin. Pharmacol.,1980, 20, 326–331].
The estimated minimum lethal dose is 15 g. Plasma concentrations greater than 300 mg/L are likely to produce toxic effects and concentrations greater than 500 mg/L are associated with moderate to severe intoxication.
In 80 subjects who had ingested an overdose of salicylate either in the form of aspirin tablets (n=42) or as topical medicaments containing methyl salicylate or wintergreen oil (n=38), the plasma salicylate concentrations on admission to hospital were generally higher in the subjects who had ingested aspirin tablets, although the 2 highest readings (4.3 and 3.5 nmol/L) belonged to subjects who had taken topical medicaments [T. Y. Chan,Postgrad. Med. J.,1996, 72, 109–112].
A blood salicylic acid concentration of 6.04 mmol/L was reported in a patient with psoriasis 19 h after he had applied 40% salicylic acid ointment to approximately 41% of his body surface; following haemodialysis, the patient was discharged after 14 days [J. Pec et al.,Cutis,1992, 50, 307–309].
Plasma half–life, dose–dependent (2 to 4 h after salicylate doses of less than 3 g, increasing to about 19 h after large doses).
Volume of distribution.
About 0.1 to 0.2 L/kg (dose–dependent).
In plasma, about 50 to 90% (dose–dependent, about 90% bound at concentrations below 100 mg/L, decreasing to 50% at concentrations above 400 mg/L).
For a review of the pharmacokinetics of salicylates see C. J. Needs and P. M. Brooks,Clin. Pharmacokinet.,1985, 10, 164–177; for a review of drug interactions involving aspirin and salicylic acid, see J. O. Miners,Clin. Pharmacokinet.,1989, 17, 327–344; for a brief review of ototoxicity associated with salicylates, see J. A. Brien,Drug Saf.,1993, 9, 143–148.
Salicylic acid is applied topically in concentrations usually ranging from 1 to about 6% as a keratolytic; up to 60% is used as a caustic in preparations for the removal of warts. Sodium salicylate is given by mouth in doses of up to 5.4 g daily.