Quantitation of the enantiomers of rimantadine in human plasma and urine by gas chromatography-mass spectrometry.
A gas chromatographic-mass spectrometric procedure has been developed for the quantitation in plasma and urine of the enantiomers of rimantadine, an antiviral drug effective against type A influenza. The assay utilizes derivatization with an optically active reagent, selective ion monitoring, methane negative-ion chemical ionization (NICI) mass spectrometry and stable isotope dilution. The method has been used to measure concentrations of each rimantadine enantiomer over a range of 2.5-250 and 12.5-1250 ng/ml in the plasma and urine, respectively, of four male volunteers administered rimantadine. In plasma and urine, no differences were observed in the disposition of the unconjugated enantiomers. In urine, one enantiomer, but not both, was released following enzymatic hydrolysis.
Miwa
B J
BJ
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Choma
N
N
Brown
S Y
SY
Keigher
N
N
Garland
W A
WA
Fukuda
E K
EK
D000218:Adamantane / Q000031:analogs & derivatives*; D000328:Adult; D008401:Gas Chromatography-Mass Spectrometry; D005966:Glucuronidase; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008954:Models, Biological; D009097:Multienzyme Complexes; D012299:Rimantadine / Q000032:analysis* / Q000097:blood / Q000652:urine; D013237:Stereoisomerism; D013429:Sulfatases
D007202:Indicators and Reagents; D009097:Multienzyme Complexes; C023059:glusulase; D012299:Rimantadine; D013429:Sulfatases; D005966:Glucuronidase; D000218:Adamantane