Preparation and analysis of deuterium-labeled aspirin: application to pharmacokinetic studies
Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods do not permit determination of systemic bioavailability when low (less than 100 mg) doses of aspirin are administered. Deuterium-labeled aspirin (2-acetoxy(3,4,5,6-/sup 2/H4)benzoic acid) was synthesized from salicylic acid by catalytic exchange and subsequent acetylation. Analysis of the compounds as benzyl esters by GC-MS followed extractive alkylation from plasma. Heptadeuterated compounds were used as internal standards. Simultaneous administration of tetradeuterated aspirin intravenously with native aspirin orally to anesthetized dogs permitted kinetic studies of both aspirin and salicylic acid. The sensitivity of the method is superior to published methods using HPLC and, thus, more applicable to studies of low dose aspirin. Pulse administration of stable isotope-labeled aspirin permits detailed and repeated studies of dose-related aspirin pharmacokinetics in humans.
- Research Organization:
- Vanderbilt Univ., Nashville, TN
- OSTI ID:
- 5095213
- Journal Information:
- J. Pharm. Sci.; (United States), Vol. 2
- Country of Publication:
- United States
- Language:
- English
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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
ACETYLSALICYLIC ACID
BIOSYNTHESIS
CHEMICAL PREPARATION
DEUTERIUM COMPOUNDS
BIOLOGICAL AVAILABILITY
DOGS
KINETICS
PHARMACOLOGY
ANALGESICS
ANIMALS
ANTIPYRETICS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HYDROGEN COMPOUNDS
HYDROXY ACIDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
SYNTHESIS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques
400702 - Radiochemistry & Nuclear Chemistry- Properties of Radioactive Materials