title: Determination of remifentanil in human and dog blood by HPLC with UV detection.
abstract: Remifentanil (GI87084) is a phenylaminopiperidine derivative of the fentanyl type with a potent analgesic activity and ultra-short half-life. The N-substituted labile methyl propanoate ester group is highly susceptible to cleavage by endogenous esterases and by chemical hydrolysis. The hydrolysis is stopped by addition of 20 microliters of 50% citric acid per 1 ml of blood. The method involves a liquid extraction of chilled blood at pH 7.4 with butyl chloride and back-extraction into 0.01 M HCl. The chromatographic conditions are: column--Zorbax SB-CN 4.6 x 250 mm; mobile phase--7% acetonitrile--14% methanol in phosphate buffer (0.03 M; pH 3.0); detection--UV at 210 nm. The internal standard used was GI97559--an ethyl analogue of the drug. The method has been validated in human blood over the range of 1-200 ng ml-1 and in dog over the range 10-60, 135 ng ml-1 with the latter assay being used in a toxicological support study. Additionally, it was used to characterize the hydrolysis of the drug, the enzymes involved in the process, and ex vivo drug interactions.
authors.affiliation: Glaxo Inc. Research Institute, Research Triangle Park, NC 27709.
authors.forename: K
authors.initials: K
authors.lastname: Selinger
authors.forename: C
authors.initials: C
authors.lastname: Lanzo
authors.forename: A
authors.initials: A
authors.lastname: Sekut
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004355:Drug Stability; D006801:Humans; D010880:Piperidines / Q000097:blood*; D000077208:Remifentanil; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010880:Piperidines; D000077208:Remifentanil