title: A method for determination of dimethyl benzoylphenyl urea (BPU) in human plasma by using LC/UV.
abstract: Dimethyl benzoylphenyl urea (BPU) inhibited tubulin polymerization, caused microtubule depolymerization in vitro and demonstrated activity against solid tumors. BPU is being tested in phase I clinical trials. A rapid and specific method using LC/UV has been developed for quantitation of BPU in human heparin-containing plasma to perform pharmacokinetic and pharmacodynamic studies. BPU is extracted from plasma into acetonitrile:n-butyl-chloride using paclitaxel as the internal standard and separated on a Waters Symmetry C18 (3.9 x 150 mm, 5 microm) column with acetonitrile-water mobile phase (70:30, v/v) using isocratic flow at 1 mL/min for a run time of 5 min. Ultraviolet detection was utilized and performed at 225 nm for BPU and paclitaxel. The retention times were 1.9 min for paclitaxel and 4.1 min for BPU. Calibration curves were generated over the range of 0.01-10 microg/mL with coefficient of determination of > 0.99. The values for within-day and between-day precision were < or = 17.0% at the LLOQ and < or = 7.4% at the low, medium and high quality controls; accuracy was +/- 5.4%. Following administration of BPU 320 mg as a weekly oral dose to a patient with advanced solid tumor malignancies, the maximum plasma concentration was 2 micro g/mL and concentrations were quantifiable up to 168 h after administration. The lower limit of quantitation of 0.01 microg/mL allows for successful measurement of plasma concentrations in patients.
authors.affiliation: Division of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Yelena
authors.initials: Y
authors.lastname: Zabelina
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D008782:Methylurea Compounds / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D008782:Methylurea Compounds; C496369:dimethyl benzoylphenyl urea