SHetA2 is a flexible heteroarotinoid that has the potential to prevent and treat lung, ovarian and cervical cancer without significant toxicity. A simple and reliable high performance liquid chromatographic (HPLC) method was developed to determine SHetA2 concentrations in the lungs, reproductive organs and plasma of mice. SHetA2 was extracted from these biological matrices by solid phase and liquid-liquid extraction in the presence of 4% H3PO4 and acetonitrile followed by filtration through a Captiva® filtration plate. Drug concentrations in the filtrates were quantified by a Waters HPLC Alliance system coupled with XBridge® C18 column, guard column and UV detection at 361 nm. The mobile phase consisted of methanol and 0.25 N sodium acetate buffer (80:20, v/v) at pH: 3. SHetA2 was eluted after 5.35 and 6.14 min for tissues and plasma, respectively. Recovery of SHetA2 from biological samples was more than 95% of the spiked amount in tissues and more than 80% of the spiked amount in plasma. The limit of detection (LOD) was 0.005 μg/mL and the limit of quantitation (LOQ) was 0.025 μg/mL, which were 280 and 56 times lower than the predicted therapeutic concentration of SHetA2, respectively. The method was suitable to quantify SHetA2 concentrations in biological matrices from animal studies administering the drug by the vaginal, pulmonary and oral routes that had the purpose of determining the pharmacokinetic parameters of drug disposition. The HPLC method developed meets the ICH Harmonized Tripartite Guideline of a reliable, sensitive, reproducible and accurate method to be used in the determination of drug concentrations in biological samples.
Keywords: Cancer; Cervix; Gynecological tissues; HPLC; Lungs; Ovary; Plasma; SHetA2; Validation.
Copyright © 2019 Elsevier B.V. All rights reserved.