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.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Selinger K,Lanzo C,Sekut Adoi
10.1016/0731-7085(94)90035-3subject
Has Abstractpub_date
1994-02-01 00:00:00pages
243-8issue
2eissn
0731-7085issn
1873-264Xpii
0731-7085(94)90035-3journal_volume
12pub_type
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