Chiral high-performance liquid chromatographic analysis of the enantiomers of XK469, a new antitumor agent, in plasma and urine

Journal of Pharmaceutical and Biomedical Analysis
Hui ZhengKenneth K Chan

Abstract

XK469 (NSC697887), (+/-)-2-[4-(7-Chloro-2-quinoxaliny)oxy]-phenoxy propionic acid, an analog of the herbicide Assure(R), which possesses antitumor activity, especially against murine solid tumors and human xenografts, has recently been found to be the first topoisomerase II beta poison. Both R(+) and S(-) isomers are cytotoxic, although the R-isomer is more potent. A chiral high-performance liquid chromatography (HPLC) assay that utilizes Chirobiotic T column for the measurement of enantiomers of XK469 in plasma has been developed with a limit of quantitation (LOQ) of 0.2 microg/ml using a 0.2 ml plasma sample. Chloroqinoxaline sulfonamide (CQS) was used as the internal standard and the assay has been validated in rat plasma. The within-run coefficient of variations (CVs) were 5.9, 5.0, and 3.1% for the S-isomer and 8.1, 4.2, 6.4% for R(+)-XK469 at 0.2, 1, and 2 microg/ml, respectively. The between-run CVs were 10.5, 5.3, and 1.9% for S(-)- and 10.9, 6.3, and 3.6% for R(+)-XK469. Using this chiral assay, a plasma concentration time data of R(+)-,S(-)-XK469 in a Fischer 344 rat receiving i.v. dosing of S(-)XK469 at 10 mg/kg was monitored. S(-)XK469 was found to be significantly converted to the R-enantiomer in circulation even w...Continue Reading

References

Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·H GaoR M Snapka
Apr 15, 2000·Journal of Pharmaceutical and Biomedical Analysis·J HeP Liu

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Citations

Jul 25, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Samir D UndeviaMark J Ratain
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hui ZhengKenneth K Chan

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