Institution: | a Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Box 600, Volker Hall 101, University of Alabama at Birmingham, Birmingham, AL 35294, USA b BioCryst Pharmaceuticals Inc., Birmingham, AL 35244, USA |
Abstract: | 9-(3-Pyridylmethyl)-9-deazaguanine (BCX-34), a new purine nucleoside phosphorylase inhibitor, has selective immunosuppressive activity with potential therapeutic value in T-cell-mediated diseases. We now report a sensitive, specific and reproducible method for measurement of 9-(3-pyridylmethyl)-9-deazagunanine in biological fluids using high-performance liquid chromatography (HPLC). 9-(3-Pyridylmethyl)-9-deazagunanine was extracted from plasma using perchloric acid precipitation followed by passage through Sep-Pak C18 cartridges (average extraction efficiency, 64.6%). Standard curves were linear over the range of interest (28–1120 ng/ml in plasma and 200–4000 ng/ml in urine, r2>0.999). Within-day and between-day coefficients of variation were less than 8%. The limit of quantitation was 28 ng/ml in plasma and 200 ng/ml in urine. This HPLC method should be useful in future clinical studies with this drug. |