Measurement of WR-1065 in plasma: preliminary pharmacokinetics in the beagle.
Described is a high-performance liquid chromatographic (HPLC) method for the quantification of WR-1065 [2-(3-aminopropylamino)-ethanethiol] in plasma. After a brief sample preparation, the drug and internal standard were separated in less than 15 minutes using a reversed-phase column and ion-pairing reagent. An electrochemical detector provided a minimum quantifiable limit of 0.05 microgram/mL. The analytical method was applied in three experiments to measure drug concentrations in the plasma of beagle dogs following IV administration of WR-1065 (60 mg/kg). The concentration-time data, best described by a three-compartment open kinetic model, were used to estimate pharmacokinetic parameters. Mean values were: steady state volume of distribution--2.27 L X kg-1; clearance--0.064 L X min-1 X kg-1; and terminal elimination half-life--81.4 min. The high clearance is consistent with the formation of mixed disulfides in the circulation.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000032:analysis; D004285:Dogs; D004355:Drug Stability; D007700:Kinetics; D008297:Male; D008624:Mercaptoethylamines / Q000097:blood*; D011837:Radiation-Protective Agents / Q000097:blood*
D004220:Disulfides; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane