Preclinical pharmacokinetics of a promising antineoplastic prototype piperazine-containing compound (LQFM018) in rats by a new LC-MS/MS bioanalytical method.
| Autor: | Rodrigues AR; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil., Rodrigues CR; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil., Gomes SA; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil., Marques SM; Institute of Biological Sciences, Federal University of Goias, Goiania, Goias, Brazil., Naves LM; Institute of Biological Sciences, Federal University of Goias, Goiania, Goias, Brazil., Pedrino GR; Institute of Biological Sciences, Federal University of Goias, Goiania, Goias, Brazil., de Oliveira-Neto JR; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil., de Carvalho FS; Medicinal Pharmaceutical Chemistry Laboratory, School of Pharmacy, Federal University of Goias, Goias, Brazil., Cruz A; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil. Electronic address: lccunha@ufg.br., Lião LM; Nuclear Magnetic Resonance Laboratory, Chemistry Institute, Federal University of Goias, Goiania, Goias, Brazil., Menegatti R; Medicinal Pharmaceutical Chemistry Laboratory, School of Pharmacy, Federal University of Goias, Goias, Brazil., Carlos da Cunha L; Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Goiania, Goias, Brazil. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2023 May 15; Vol. 1223, pp. 123710. Date of Electronic Publication: 2023 Apr 12. |
| DOI: | 10.1016/j.jchromb.2023.123710 |
| Abstrakt: | LQFM018 is a novel antineoplastic prototype, showing an expressive drug-triggered K562 leukemic cells death mechanism, through necroptotic signaling. Due to its promising effect, this study aimed to evaluate the pharmacokinetics of LQFM018 in rats, using a new validated bioanalytical LC-MS/MS-based method. Chromatographic column was an ACE® C18 (100 mm × 4.6 mm, 5 µm) eluted by a mobile phase composed of ammonium acetate 2 mM and formic acid 0.025%:methanol (50:50, v/v), under flow of 1.2 mL/min and injection volume of 3.0 µL. LQFM018 was extracted from rat plasma by a simple liquid-liquid method, using MTBE solvent. Rats were administered intraperitoneally at LQFM018 100 mg/kg dose and blood samples were collect at times of 0, 1, 2, 3, 4, 5, 6, 7, 8, and 9 h. Bioanalytical-LC-MS/MS-based method was rapid, high throughput and sensitive with a good linearity ranging from 10 (LLOQ) to 15000 ng/mL, besides precise and accurate, ranging of 0.8-7.3% and 96.8-107.6%, respectively. The prototype LQFM018 was rapid and well absorbed, and highly distributed, apparently due to its high lipid solubility. These features are primordial for an anticancer agent in the treatment of deep tumors, such as bone marrow neoplasms, in which the drug might permeate easily tissue barriers. Also, LQFM018 has demonstrated a high clearance, according to a low t Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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