Measurement of WR-1065 in plasma: preliminary pharmacokinetics in the beagle.

Autor: Swynnerton NF, Huelle BK, McGovern EP, Mangold DJ, Ludden TM
Jazyk: angličtina
Zdroj: Research communications in chemical pathology and pharmacology [Res Commun Chem Pathol Pharmacol] 1986 Nov; Vol. 54 (2), pp. 255-69.
Abstrakt: 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.
Databáze: MEDLINE