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Analysis of 2-(3-methyl-4-aminophenyl)-benzothiazole (NSC 674495) in plasma by gas chromatography with mass-selective
L R Phillips1, C Bramhall, J Buckley
1Laboratory of Drug Discovery, Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick, MD 21701, USA. Phillips@dtpax2.ncifcrf.gov
Abstract:
Certain naturally occurring isoflavonoids have been shown to inhibit protein-tyrosine kinases, and this has led to investigations of ring-modified structural analogs. Most recently, 2-(3-methyl-4-aminophenyl)-benzothiazole (MAB: NSC 674495) was shown to possess significant activity against certain breast cell cancer lines in vitro and in vivo. Our efforts thus focussed on developing a simple and sensitive method for quantitating MAB in plasma using GC-MS. The GC-MS assay was found to be linear over the range of 0.050 to 5.0 microg/ml, and was applied to monitor the plasma concentration of MAB in a rat dosed with 25 mg/kg as a 1 min intravenous infusion. Plasma was collected at intervals from 3 through 180 min, and concentrations of MAB were determined. Non-linear regression analysis of the plasma concentration-time data revealed that levels declined from a maximum at 3 min of 18 microg/ml to 1 microg/ml at 3 h in a biphasic manner. In another investigation, significant plasma concentrations of a major metabolite was detected and determined to be mono-N-acetylated MAB.