No abstract

CI-973 is a new platinum compound with antitumor properties that is currently undergoing phase II clinical trials. A high-performance liquid chromatographic (HPLC) assay was developed and validated for ultrafiltrates of human plasma and urine to support phase I clinical trials. Plasma ultrafiltrate (0.5 ml) was extracted using C18 solid-phase cartridges. Urine was diluted 10-fold and extracted first with SAX solid-phase cartridges and then with C18 cartridges. For both matrices, the eluate from the C18 cartridges was injected directly. A Whatman PAC 10 column (4.6 x 250 mm, 10-microns particle size) and ultraviolet detection at 205 nm were used for both analyses. The mobile-phase buffer was 0.05 M sodium perchlorate (pH 2.3). The mobile-phase acetonitrile:buffer ratio, column temperature, and flow rate were 89:11 (v/v), 40 degrees C, and 2.0 ml/min, respectively, for the plasma ultrafiltrate assay and 85:15 (v/v), 50 degrees C, and 1.0 ml/min, respectively, for the urine ultrafiltrate assay. Standard curves were linear from 0.25 to 500 micrograms/ml and from 1.0 to 250 micrograms/ml for the plasma and urine assays, respectively. The accuracy of the assay lay within 4.5% of the nominal values, and the precision was 6.2%; the recovery of CI-973 varied from 79.2% to 105%. CI-973 remains stable in plasma for at least 6 h, at room temperature, in ultrafiltrates of both matrices for at least 15 days at -72 degrees C, and in water for at least 6 months at -72 degrees C.

A Zymark XP Robot has been adapted to extract a novel anti‐inflammatory drug (CI‐1004) and internal standard (IS) from rat plasma using a batch robotic solid‐phase extraction system. Under computer control, the robot automatically conditions, loads, washes, and elutes up to 144 solid‐phase cartridges in parallel. The system incorporates a miniature pressure transducer to monitor and control manifold vacuum, thereby controlling solvent flow through the cartridges. Liquid chromatographic separation was achieved isocratically on a Zorbax Rx‐C8 analytical column (4.6 mm i.d. × 250 mm). Mobile phase consisted of 65:35 (v/v) acetonitrile and 20 mM ammonium acetate (pH = 4.0). Column effluent was monitored spectrophotometrically at 360 nm. Specificity, chromatographic performance parameters, system repeatability, recovery from matrix, linearity, precision, and accuracy were evaluated. No interfering peaks were observed at the retention time of CI‐1004 throughout the validation process. Peak‐height ratios were proportional to CI‐1004 in rat plasma over the concentration range of 7.5‐5000 ng/mL. The system is capable of extracting 100 plasma samples in approximately 5 hours. © 1996 John Wiley & Sons, Inc.

No abstract