AN HPLC ASSAY UTILIZING SOLID-PHASE EXTRACTION FOR CI-1010, AN ALKYLATING RADIOSENSITIZER, IN RAT PLASMA

CI-1010, a 2-nitroimidazole, is a chiral prodrug for the active moiety PD 146923 and is under development as an alkylating radiosensitizer t o be used as an adjuvant to radiotherapy. Because CI-1010 has an estim ated half-life less than or equal to 2 min under physiological conditi ons its metabolites/degradation products PD 146415, an inactive moiety , and PD 146923 were assayed to support rat toxicology studies. The me thod involves the processing of plasma samples through phenyl solid-ph ase extraction cartridges followed by chromatography on CN columns wit h UV detection at 325 nm. The assay appears linear over the range 0.05 0-100 mu g ml(-1) for both PD 146415 and PD 146923. Interrun accuracy and precision estimates for PD 146415 and PD 146923 were within +/- 6. 50 and less than or equal to 3.27%, respectively, and +/- 12.8 and les s than or equal to 4.06%, respectively, for quality controls containin g nominal concentrations of 0.400, 4.00 and 40.0 mu g ml(-1). The abso lute recovery of CI-1010, PD 146415 and internal standard, PD 126675, were approximately 40, 96 and 95%, respectively. The recovery of PD 14 6923 appeared concentration dependent and ranged from 68 to 92%. PD 14 6145 and PD 146923 were both stable in rat plasma at 4 degrees C and - 77 degrees C for at least 7 h and 154 days, respectively. CI-1010 was not stable in rat plasma at 4 degrees C. CI-1010, PD 146145 and PD 126 675 were stable for at least 63 days in 10 mM phosphate buffer at pH 3 .0 and 4 degrees C. Under identical conditions PD 146923 was stable fo r only 8 days. The applicability of this method to determine concentra tions of PD 146145 and PD 146923 in rat plasma is reported in this pap er. (C) 1997 Elsevier Science B.V.