A radioimmunoassay for the new antiviral agent 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil.
A specific and sensitive radioimmunoassay (RIA) for the measurement of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in biological fluids has been developed. The assay has a range of 2.5-1,000 ng/ml and 10-1,000 ng/ml for serum and urine, respectively, and has the sensitivity to detect 2.5 and 25 ng/ml of BV-araU in serum and urine, respectively. A satisfactory zero binding and sensitivity were obtained after an overnight incubation at 4 degrees C. Separation of the antibody-bound and free ligand was achieved by employing polyethylene glycol-goat anti-rabbit gamma globulin separant. A quantitative recovery of the exogenous analyte was obtained at all concentrations of BV-araU tested. The assay is specific for the parent drug and is not affected by the presence of its metabolite, BV-U (bromovinyl uracil) or serum components (nucleotides, nucleosides, or sugars). Intraassay coefficients of variation were 3.1-4.4% and 2.5-4.2% for serum and urine controls, respectively. Interassay variability was < 8.6% for all serum and urine controls. Linear regression analysis showed that the correlation between RIA and high-pressure liquid chromatography was excellent (r = 0.997). The ascending dosage studies have been analyzed by the BV-araU RIA, and results indicate that the values of area under the serum concentration-time curve increased proportionally with the administered dose of BV-araU up to 80 mg. Cumulative urinary excretion data showed that approximately 50% of unchanged BV-araU was excreted in the urine within 24 h.
Jagoda
E
E
Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903-0191.
Ogan
M
M
Stouffer
B
B
Tsay
H M
HM
Turabi
N
N
Mantha
S
S
Yost
F
F
Tu
J I
JI
D000998:Antiviral Agents / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents / Q000138:chemical synthesis; D007553:Isotope Labeling; D008297:Male; D011863:Radioimmunoassay / Q000379:methods; D012015:Reference Standards; D012680:Sensitivity and Specificity
D000998:Antiviral Agents; D007202:Indicators and Reagents; D001086:Arabinofuranosyluracil; C031368:sorivudine