Clinical pharmacology of an atrasentan and docetaxel regimen in men with hormone-refractory prostate cancer.

Purpose: This study was conducted to evaluate potential pharmacokinetic interactions between docetaxel and atrasentan as part of a phase I/II clinical trial.

Methods: Patients with prostate cancer were treated with intravenous docetaxel (60-75 mg/m(2)) every 3 weeks and oral atrasentan (10 mg) daily starting on day 3 of cycle 1 and then given continuously. The pharmacokinetics of both drugs were evaluated individually (cycle 1, day 1 for docetaxel; day 21 for atrasentan) and in combination (cycle 2, day 1 for both drugs).

Development and utilization of a combined LC-UV and LC-MS/MS method for the simultaneous analysis of tegafur and 5-fluorouracil in human plasma to support a phase I clinical study of oral UFT®/leucovorin.

Tegafur is a 5-fluorouracil (5-FU) prodrug widely used outside the United States to treat colorectal cancer as well as cancers of the head and neck. The resulting plasma concentrations of tegafur are much higher than those of 5-FU; thus, analytical methods are needed that are sensitive enough to detect low plasma concentrations of 5-FU and robust enough to simultaneously analyze tegafur. Previous LC-MS/MS methods have either failed to demonstrate the ability to simultaneously measure low 5-FU and high tegafur plasma levels, or failed to be applicable in clinical studies.

Identification of isobaric product ions in electrospray ionization mass spectra of fentanyl using multistage mass spectrometry and deuterium labeling.

Isobaric product ions cannot be differentiated by exact mass determinations, although in some cases deuterium labeling can provide useful structural information for identifying isobaric ions. Proposed fragmentation pathways of fentanyl were investigated by electrospray ionization ion trap mass spectrometry coupled with deuterium labeling experiments and spectra of regiospecific deuterium labeled analogs. The major product ion of fentanyl under tandem mass spectrometry (MS/MS) conditions (m/z 188) was accounted for by a neutral loss of N-phenylpropanamide.