Quantitative determination of the gamma-aminobutyric acid agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, in serum by high-performance liquid chromatography.
A method was developed to determine pharmacologically relevant concentrations of the gamma-aminobutyric acid agonistic compound THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) in serum. THIP is extracted from serum by a cation-exchange column, derivatized by dansyl chloride, and further separated and quantitated by reversed-phase high-performance liquid chromatography using measurement of ultraviolet absorption at the optimal wave-length (265 nm). The lower detection limit of the method is 0.07 mumol 1(-1) (10 ng ml-1) when 2 ml of serum are used for extraction. This sensitivity is sufficient for pharmacokinetic studies in man following administration of a presumably therapeutic dose of THIP. Blood samples collected from 28 patients treated with one or more of 26 drugs relevant for coadministration with THIP did not contain substances which would affect the reliable quantitation of THIP, if present.
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D002852:Chromatography, Ion Exchange; D004285:Dogs; D006801:Humans; D007555:Isoxazoles / Q000097:blood* / Q000302:isolation & purification; D007700:Kinetics; D010080:Oxazoles / Q000097:blood*; D010215:Papio; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007555:Isoxazoles; D010080:Oxazoles; D005680:gamma-Aminobutyric Acid; C015542:gaboxadol