Analysis of 2-(3-methyl-4-aminophenyl)-benzothiazole (NSC 674495) in plasma by gas chromatography with mass-selective detection.

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.

• Authors: L R Phillips, C Bramhall, J Buckley, T W Daw, S F Stinson
• Journal: Journal of chromatography. B, Biomedical sciences and applications (J Chromatogr B Biomed Sci Appl) Vol. 732 Issue 2 Pg. 315-21 (Sep 24 1999) ISSN: 1387-2273 [Print] Netherlands
• PMID: 10517353 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Aniline Compounds
• Antineoplastic Agents
• Benzothiazoles
• NSC 674495
• Thiazoles

Topics

• Aniline Compounds (blood, pharmacokinetics)
• Animals
• Antineoplastic Agents (blood, metabolism, pharmacokinetics)
• Benzothiazoles
• Calibration
• Gas Chromatography-Mass Spectrometry (methods)
• Humans
• Quality Control
• Rats
• Reproducibility of Results
• Sensitivity and Specificity
• Thiazoles (blood, pharmacokinetics)