Simultaneous quantification of an anti-inflammatory compound (DuP 697) and a potential metabolite (X6882) in human plasma and urine by high-performance liquid chromatography.
A high-performance liquid chromatographic (HPLC) method using fluorescence detection has been developed for the simultaneous analysis of low nanogram concentrations of an anti-inflammatory drug, 5-Bromo-2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]thiophene (DuP 697), and a potential metabolite (X6882) in human plasma and of DuP 697 in human urine. This assay method used an EM Separations Lichrospher C18 endcapped column. The mobile phase was acetonitrile-water (75:25, v/v). The detection of DuP 697 and X6882 was by fluorescence at excitation and emission wavelengths of 256 and 419 nm, respectively. The chromatographic system could separate DuP 697 from X6882, the external standard (anthracene), and other endogenous substances present in human plasma. In human plasma the limits of quantification for DuP 697 and X6882 were 3 and 20 ng/ml, respectively; the limit of quantification for DuP 697 in human urine was 5 ng/ml. These compounds were shown to be stable in frozen (-20 degrees C) human plasma and urine for at least 9 weeks. The assay described has been used to characterize DuP 697 pharmacokinetics after oral administration in humans.
Drug Metabolism and Pharmacokinetics Section, DuPont Merck Pharmaceutical Company, Newark, DE 19714.
A S
AS
Joshi
N
N
Raghavan
R M
RM
Williams
K
K
Takahashi
H
H
Shingu
S Y
SY
King
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005615:Freezing; D006801:Humans; D013050:Spectrometry, Fluorescence; D013696:Temperature; D013876:Thiophenes / Q000032:analysis* / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013876:Thiophenes; C092104:X 6882; C064874:DuP 697