High performance liquid chromatographic analysis and preclinical pharmacokinetics of the heteroarotinoid antitumor agent, SHetA2

Cancer Chemotherapy and Pharmacology
Yilong ZhangKenneth K Chan

Abstract

SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methane-thione], NSC 726189} is a sulfur-containing heteroarotinoid, which selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective was to develop and validate a HPLC/UV method for the determination of SHetA2, and study the pharmacokinetics of SHetA2 in the mouse. SHetA2 and the internal standard, methylated XK469 (MeXK469) were isolated from 0.2 ml of mouse plasma by solid phase extraction. The analytes were separated on a narrow-bore C18 column, with the mobile phase consisting of 60% acetonitrile in water at a flow rate of 0.2 ml/min. UV detection was set at 341 nm. Pharmacokinetic studies of SHetA2 were carried out in mice following i.v. bolus dose at 20 mg/kg and oral administrations at 20 and 60 mg/kg. The standard curves were linear between 25 and 2,500 nM and the lower limit of quantification (LLOQ) was 25 nM. The within-run coefficients of variation (CVs) were 11.1% at 10, 9.4% at 100, and 5.2% at 2,500 nM and the respective between-run CVs were 10.9, 3.1, and 1.5% (all n=5). The recovery was 85.8% for SHetA2 and 80.6% for MeXK469. Following i.v. bolus dose, plasma co...Continue Reading

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Citations

Nov 13, 2008·Cancer Chemotherapy and Pharmacology·Dorleta OtaeguiJosé Luis Pedraz
Sep 20, 2008·Investigational New Drugs·Tashanna MyersDoris M Benbrook
May 7, 2009·Molecular Cancer Therapeutics·Tongzu LiuDoris Mangiaracina Benbrook
Nov 21, 2013·Investigational New Drugs·Doris Mangiaracina BenbrookK Darrell Berlin
Apr 17, 2015·European Journal of Medicinal Chemistry·Krishna Kumar GnanasekaranK Darrell Berlin
Dec 24, 2017·Investigational New Drugs·Doris M BenbrookChinthalapally V Rao
Dec 18, 2019·International Journal of Cancer. Journal International Du Cancer·Satish K RamrajDoris M Benbrook
Jul 16, 2013·Cancer Prevention Research·Doris Mangiaracina BenbrookChinthalapally V Rao
Jun 3, 2021·Cancers·Vishal ChandraDoris Mangiaracina Benbrook

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