Analysis of 2-(3-methyl-4-aminophenyl)-benzothiazole (NSC 674495) in plasma by gas chromatography with mass-selective detection.
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.
Phillips
L R
LR
Laboratory 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
Bramhall
C
C
Buckley
J
J
Daw
T W
TW
Stinson
S F
SF
D000814:Aniline Compounds / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D052160:Benzothiazoles; D002138:Calibration; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D011786:Quality Control; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000097:blood* / Q000493:pharmacokinetics
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D052160:Benzothiazoles; C122062:NSC 674495; D013844:Thiazoles