NLCQ-1 (NSC 709257) is a weak DNA-binding bioreductive antiproliferative agent, with potent in vitro antiproliferative activity against rodent and human tumor cell lines under aerobic and anaerobic conditions. Interest in this quinoline analog is based in part on its in vivo synergistic antitumor effect with radiotherapy or chemotherapy against mouse tumors and human xenografts. A sensitive, specific HPLC method was developed to measure NLCQ-1 in biological fluids. Calibration curves were linear in the range 10.4-667 ng/ml and the lower limit of quantitation was 10.4 ng/ml in plasma. NLCQ-1 was stable in organic solvents, buffered solutions and human plasma for 24 h at 37 degrees C. NLCQ-1 was unstable in rodent and dog plasma when incubated for longer than 10 h. NLCQ-1 human plasma protein binding was high (about 99%), and included binding to both alpha(1)-acid glycoprotein and serum albumin. The plasma elimination of NLCQ-1 in mice after a 10-mg/kg intravenous bolus dose was described by a two-compartment open model with t(1/2beta), V(ss), and Cl(TB) values of 41.3 min, 2.04 l/kg and 69.9 ml/min per kg, respectively. NLCQ-1 had high (85%) intraperitoneal and modest (28%) oral relative bioavailability. Little of the administered NLCQ-1 dose (6.4%) was excreted in 24-h urine. The mouse pharmacokinetic data suggested that oral administration may achieve plasma concentration and systemic exposure similar to those observed after intravenous administration of NLCQ-1.