Accession Number : ADB093467

Title :   Development of Analytical Methods for the Determination of Drug Substances in Biological Fluids.

Descriptive Note : Annual rept. 1 Oct 82-31 Aug 83,

Corporate Author : CALIFORNIA UNIV SAN FRANCISCO SCHOOL OF PHARMACY

Personal Author(s) : Lin,E. T. ; Benet,L. Z. ; Upton,R. A. ; Gee,W. L.

Report Date : 26 AUG 1983

Pagination or Media Count : 21

Abstract : WR6026 2HCl (6-methoxy-8-(6-diethyl amino hexyl amino) (epidine dihydrochloride) is a very effective antileishmanial drug in hamsters infected with L donovani. A high pressure liquid chromatographic (HLPC) procedure for the analysis of WR6026 in plasma has been developed. Only 0.5 mil of plasma is required for analysis. The clean-up procedure involves a protein precipitation step and a column elution stem prior to separation by HPLC. The assay is quite sensitive with a detection limit of less than 10 ng/ml of plasma. Assay precision has been evaluated and variability is less than 6%. Accuracy was evaluated from blind samples in the range of 10-100 ng/mL and the difference was 1.13 - 8.04%. Stability was also determined for WR6026 in plasma frozen for up to three months. Human plsma samples were analyzed for WR6026; the drug could be detected up to 24 hours following a 60 mg oral dose. In a preliminary study with human volunteers, no mono-N-deethylated derivative of WR6026 was found in human plasma. This assay is suitable for pharmacokinetic studies involving WR6026 in human subjects.

Descriptors :   *ANTIPARASITIC DRUGS, *BLOOD ANALYSIS, *LIQUID CHROMATOGRAPHY, BIOASSAY, ACCURACY, SAMPLING, HIGH PRESSURE, HUMANS, VOLUNTEERS, PRECIPITATION, PROTEINS, HAMSTERS, BLOOD PLASMA, PHARMACOKINETICS

Subject Categories : Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE