Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatography assay for the novel antitumour agent CT2584 in human plasma

Khan, Parveen; Abbas, Sayara; Cheeseman, Susan L.; Ranson, Malcolm R; McGown, Alan T.

doi:10.1016/s0378-4347(98)00491-5

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…CT-2584 HMS content was determined by the Bioanalytical Chemistry Department of Covance Laboratories Inc, Wisconsin using an HPLC method with ultra-violet (UV) detection. A validation system was developed 'in house' and duplicate samples analysed (Khan et al, 1999). CT-2584 HMS was extracted into potassium phosphate extraction buffer and methyl-t-butyl ether from human plasma.…”

Section: Sample Collection and Drug Analysismentioning

confidence: 99%

Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours

Cheeseman

Brannan²,

McGown

et al. 2000

Br J Cancer

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Summary CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean C max and AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (C max and AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of V d and clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m 2 because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m 2 daily × 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination.

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Section: Sample Collection and Drug Analysismentioning

confidence: 99%