title: High-performance liquid chromatographic determination of 9-(3-pyridylmethyl)-9-deazaguanine (BCX-34) in biological fluids.
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 disease. We now report a sensitive, specific and reproducible method for measurement of 9-(3-pyridylmethyl)-9-deazaguanine in biological fluids using high-performance liquid chromatography (HPLC). 9-(3-Pyridylmethyl)-9-deazaguanine 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Alabama at Birmingham 35294, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: G M
authors.initials: GM
authors.lastname: Walsh
authors.forename: R H
authors.initials: RH
authors.lastname: Wheeler
authors.forename: R B
authors.initials: RB
authors.lastname: Diasio
mesh_terms: D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D007262:Infusions, Intravenous; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood / Q000188:drug therapy / Q000652:urine; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy / Q000652:urine
chemical_list: D007166:Immunosuppressive Agents; D006147:Guanine; C104194:peldesine; D011683:Purine-Nucleoside Phosphorylase