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  • Title: Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatographic assay for the novel bio-reductive anti-tumor agent RH1 in human and mouse plasma.
    Author: Khan P, Abbas S, Hargreaves RH, Caffrey R, Megram V, McGown A.
    Journal: J Chromatogr B Biomed Sci Appl; 1999 Jun 11; 729(1-2):287-95. PubMed ID: 10410954.
    Abstract:
    A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the experimental anticancer agent, RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) which is currently being evaluated by the CRC phase I/II committee. A 500 mg amino propyl solid-phase extraction cartridge was used to isolate RH1 from human plasma. Analysis was performed on a reversed-phase chromatography system using a 15 cm cyanopropyl column and isocratic elution with a 10% methanol-90% water (double distilled) solution. The lower limit of quantitation for RH1 was found to be 0.00375 microg/ml (3.75 ng/ml+/-8.3%) in water and following extraction from plasma. Recovery of >80%(+/-11.9%) was achieved over a five-day validation study. This method was used to carry out pre-clinical studies in BDF mice (standard strain of hybrid mice) at three dose levels (2, 5 and 10 mg/kg of RH1 in 0.9% (w/v) saline via an intraperotoneal injection). Standard Version of PC Winnonlin pharmacokinetic modelling software was used to model the data. A none-compartmental model was used to describe the disposition of RH1 in mice plasma. RH1 was rapidly eliminated from plasma with a mean plasma clearance of 23.4 ml/min, mean volume of distribution of 321.6 ml and mean t(1/2) alpha and beta decays of 4.8 and 9.6 min, respectively. RH1 in human and mouse whole blood and plasma was found to be stable up to 2 h.
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