Identification and simultaneous determination of p-FHA and p-FBA, two metabolites of anti-tumor agent--Fluorapacin in rat urine.
Fluorapacin, bis(4-fluorobenzyl)trisulfide, a small molecule natural product derivative of trisulfide, has revealed a broad spectrum of anti-proliferative activity and in vivo anti-tumor efficacy in human xenograft mice models with excellent safety profile. In the present study, two new metabolites, para-fluorohippuric acid (p-FHA) and para-fluorobenzoic acid (p-FBA), were identified by GC-MS and HPLC as the main metabolites in urine of rats after intravenous administration of fluorapacin. A simple HPLC-UV method for simultaneous determination of these two metabolites in urine has been developed and validated. The newly developed method demonstrated excellent specificity, accuracy, precision, and stability. This method was successfully employed to study the urinary excretion of fluorapacin in rats. The results indicated that p-FHA was the major metabolite in urine, and the total excretion recovery of p-FHA and p-FBA was 67.6+/-4.9% (mean+/-SE, n=6) of dosage after 48h of administration.
Pan
Hao
H
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Zhou
Hui
H
Zeng
Su
S
Xu
Xiao
X
An
Haoyun
H
Jiang
Huidi
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001565:Benzoates / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006626:Hippurates / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000493:pharmacokinetics*
C541416:4-fluorohippuric acid; D000970:Antineoplastic Agents; D001565:Benzoates; D005464:Fluorobenzenes; D006626:Hippurates; D013440:Sulfides; C528265:fluorapacin; C022893:4-fluorobenzoic acid