Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of ARQ 501 (beta-lapachone) in plasma and tumors from nu/nu mouse xenografts

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
R E SavageT C K Chan

Abstract

A sensitive and specific LC-MS/MS method employing positive electrospray ionization for the determination of ARQ 501 (beta-lapachone) in (nu/nu) mouse plasma and tumor tissue is described. Samples were processed using protein precipitation with acetonitrile. A d6 analog of ARQ 501 was used as the internal standard (IS). The analytes were separated using a Zorbax SB8 column (30 mm x 2.1 mm i.d. 5 microm particle size) and analyzed in the multiple reaction monitoring (MRM) mode using mass transitions of 243>159 and 249>159 m/z for ARQ 501 and d6-ARQ 501, respectively. The lower limit of quantitation (LLOQ) for ARQ 501 was 3.0 ng/mL. The calibration curve was linear in the range of 3.0-2000 ng/mL with a correlation coefficient better than 0.99. Intra- and inter-batch precisions were within 8.4% for plasma and 11.8% for tumor samples. Accuracy expressed as percentage relative error (%R.E.) ranged from -9.0 to 7.7 for both plasma and tumor samples. Recovery was between 106 and 113% for both ARQ 501 and its d6 analog. Plasma pharmacokinetic data of ARQ 501 in mouse from intraperitoneal (IP) dosing at 60 mg/kg obtained using this validated method is presented along with tumor concentration data. The C(max), AUC(0-infinity), t(1/2), Cl...Continue Reading

References

Aug 1, 1984·Journal of Medicinal Chemistry·K Schaffner-SabbaJ W Wasley
Apr 20, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kathryn E ReinickeDavid A Boothman

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